Honeybee Repellents and Uses Thereof

ABSTRACT

The present specification discloses honeybee repellents exhibiting repellent properties similar to 2-heptanone, compositions comprising such repellents, uses to repel a honeybee from a mammal, location, plant, structure treated of such repellents, and methods of treating a mammal, location, plant, structure by applying such repellents.

This patent application claims priority pursuant to 35 U.S.C. §119(e) toU.S. Provisional Patent Application 61/819,422, filed May 3, 2013, whichis hereby incorporated by reference in its entirety.

Portions of the work described herein were supported by Small BusinessInnovation Research (SBIR) grant numbers 0611005, 0810785, and 0956877awarded by the National Science Foundation (NSF). The government of theUnited States of America may retain certain rights to this patent.

Honeybees use scent marks while foraging. When collecting nectar and/orpollen, foraging honeybees scent mark nectar-producing flower bydepositing attractive pheromones to signal to other honeybees of anearby rewarding food source. Honeybees also use a short-lived repellentscent mark that identifies exhausted and recently visited rewardingflowers not yet replenished with nectar. Subsequently visiting honeybeesdetect and avoid these nectar-depleted flowers. Over time, as nectarreplenishes in the flower, the repellent scent mark fades until gone andthe flower is eventually revisited by another foraging honeybee. It ispresumed that the use of repellent scent marks increases foragingefficiency by reducing the time spent probing nectar-depleted flowers.

The repellent scent mark used by honeybees is 2-heptanone. Produced andsecreted by the mandibular glands of adult worker honey bees,2-heptanone is known as the alarm pheromone because under certaincircumstances elicits aggressive behavior in honeybees when detected.Honeybees detect 2-heptanone using an olfactory pathway mediated by aspecific odorant-binding protein called OBP2. By taking advantage of itsproperties, repellent formulation of 2-heptanone have been produced andused in agricultural settings. For example, 2-heptanone has been appliedto crops in order to repel honeybees away from areas where toxicinsecticides have also been applied, thereby reducing honeybee mortalityand avoiding potential insecticide contamination of the colony and thehive products obtained thereof. However, such uses have had very limitedsuccess primarily because 2-heptanone is a considerably volatilecompound, having an effective half-life of only a few hours. As such,2-heptanone is impractical and cost-ineffective for agricultural usesbecause of the extensive efforts necessary to apply and maintain aneffective amount of this repellent in the treated area.

Therefore, what are needed are more effective honeybee repellents thatexhibit repellent properties similar to 2-heptanone, but are lessvolatile. The present specification discloses such honeybee repellentsand uses and methods for such compounds. The disclosed honeybeerepellents will benefit apiculture since honeybees are a crucial,domesticated species that is threatened by routine agriculturalpractices such as the use of insecticides.

Thus, aspects of the present specification disclose honeybee repellentsexhibiting repellent properties similar to 2-heptanone, but are lessvolatile than 2-heptanone.

Other aspects of the present specification disclose a use of a honeybeerepellent disclosed herein to repel a honeybee from a location treatedwith the honeybee repellent. In one embodiment, the disclosed use is ause of a honeybee repellent disclosed herein to repel a honeybee fromforaging and/or collecting nectar from a flower of a plant treated withthe honeybee repellent. In another embodiment, the disclosed use is ause of a honeybee repellent disclosed herein to repel a honeybee from astructure treated with the honeybee repellent.

Yet other aspects of the present specification disclose a method oftreating a location by applying a honeybee repellent disclosed herein,wherein the application repels a honeybee from the treated location. Inone embodiment, the disclosed method is a method of treating a plant byapplying a honeybee repellent disclosed herein, wherein such applicationrepels a honeybee from foraging and/or collecting nectar from a flowerof the treated plant. In another embodiment, the disclosed method is amethod of treating a structure by applying a honeybee repellentdisclosed herein, wherein such application repels a honeybee from thetreated structure.

DESCRIPTION

Honeybees are maintained by humans in order to harvest honey, beeswax,and other hive products produced by these insects for commercialmarkets. In the United States, for example, honeybees produce $270million worth of honey, beeswax, and other hive products. Besides theeconomic importance of hive products, honeybees are critically necessaryto pollinate many important agricultural crops produced worldwide. Forexample, honeybees pollinate over $14 billion worth of crops annually inthe United States. As such, promoting and maintaining honeybee survivalis of great economic importance.

Insecticides are widely used to increase the yields of agriculturalcrops and their use is one of the major factors behind the increase inagricultural productivity in the 20th century. However, there is aninherent tension between the use of insecticides on crop plants tocontrol invading pest insects and the necessity of honeybees topollinate these same plants and the economic importance of hiveproducts. One commonly used method is to delay the use of insecticidesuntil the honeybees pollination has occurred, and then apply theinsecticide. However, foraging for nectar occurs throughout the growingseason, and as such, foraging honeybees are still exposed to theinsecticide. Furthermore, recent evidence suggests that commonly usednicotine-based insecticides like Clothianidin and Imidacloprid may be acausal factor in colony collapse disorder, a phenomenon in which workerhoneybees from a colony abruptly disappear. As such, it would beextremely beneficial to develop and use compounds and methods of insectcontrol that minimize honeybee mortality.

Although of significant value, honeybee pollination can also causeeconomic harm to certain agricultural crops. For example, certainseedless citrus fruits like seedless tangerines, grapefruit, andmandarin oranges are of great economic value due to consumer preference.These seedless fruits are self-pollinating. However, if honeybeescross-pollinate the crop plants with the pollen of a seeded citrusfruit, then these citrus fruits will develop seeds and becomeundesirable to the consumer. As such, citrus fruit growers employinsecticides in order to prevent honeybee cross-pollination. The mostcommon insecticides used for this application are neonicotinoids likeClothianidin and Imidacloprid, which as discussed above, appears to be acausal factor in colony collapse disorder. One problem with thisapproach is that the nectar collected by honeybees from the flowers ofcitrus trees produces a flavorful and economically desirable honey. Assuch, beekeepers have historically kept colonies near citrus orchards.Thus, there is another inherent tension between the economic importanceof hive products produced by honeybees versus the financial harm causedby honeybee pollination in certain agricultural crops like citrus trees.As such, it would be extremely beneficial to develop and use compoundsand methods that could repel honeybees from crop plants wherepollination is undesired without causing significant honeybee mortality.

Insect chemosensory proteins (CSPs) regulate or control crucialbehaviors. The chemosensory system consists of several chemosensoryprotein (CSP) classes. Chemosensory protein classes that are importantin the design of novel insect control products include soluble proteinsfound in the antennal hemolymph and the maxillary palps, such as odorantbinding proteins (OBPs) and sensory appendage proteins (SAPs). OBPs andSAPs are carrier proteins that facilitate the transport of externalstimuli such as odor molecules through the aqueous hemolymph of sensoryappendages to the surfaces of neuronal cells. There, the protein/odorantmolecule complexes bind G-protein coupled receptors (GPCRs) and initiatea signaling cascade that results in a behavioral response to theexternal odor or stimulus. Insects use chemosensory cues from theenvironment to control critical behaviors, such as feeding and mating.Thus, insect chemosensory proteins are promising targets for thediscovery of novel insect control products based on manipulating insectbehavior.

The present specification discloses improved honeybee repellents anduses and methods for such repellents. By exploiting the OBP2 olfactorypathway used by 2-heptanone, more effective repellent compounds havebeen identified and isolated. As such, the repellents disclosed hereinmanipulate the honeybees' chemosensory system by eliciting an avoidanceresponse similar to the one initiated by 2-heptanone. The repellentsdisclosed herein are intended for agricultural, commercial, and consumeruse. For example, the honeybee repellents disclosed herein are useful torepel honeybees from areas where insecticides have also been applied inorder to reduce honeybee mortality and avoid insecticide contaminationof honey, beeswax, and other hive products. As another non-limitingexample, the honeybee repellents disclosed herein are useful to preventunwanted pollination of plants by honeybees in crops where suchpollination reduces the market value due to the resulting seeded fruits.As yet another non-limiting example, the honeybee repellents disclosedherein are useful to keep away honeybees from outdoor areas where humanactivities are occurring and would be disrupted by honeybee presence,such as, e.g., an outdoor activity like a sporting event or picnic.Similarly, the honeybee repellents disclosed herein are useful to keepaway honeybees from man-made structures in order to prevent infestationof a colony, such as, e.g., a commercial building, a house, a shed, orother structure. Other uses of the honeybee repellents disclosed hereinare discussed below and are readily apparent to a person of ordinaryskill.

Aspects of the present specification disclose a honeybee repellent. Asused herein, the term “honeybee repellent” is synonymous with “repellentcompound” and refers to a compound that mimics a 2-heptanone-specificresponse. 2-Heptanone, CH₃(CH₂)₄COCH₃, CAS Registry No. 110-43-0, alsoknown as methyl n-amyl ketone and methyl pentyl ketone, is a colorless,liquid with a banana-like, fruity odor. It is a volatile liquid at roomtemperature [d415 0.8197; b.p.₇₆₀ 151.5° C.] and soluble in alcohol orether and very slightly soluble in water. 2-Heptanone is availablecommercially.

Bees are insects of the Order Hymenoptera, Superfamily Apoidea, andcomprise a group of about 20,000 species that live throughout the world.Examples of common bees are honeybees (Apis), bumble bees (Bomzbus),small carpenter bees (Ceratina), large carpenter bees (Xylocopa), paperwasps (Polistes), yellow jackets (Vespula), and baldfaced hornets(Vespula). At least seven species of honeybee are commonly recognizedwith a total of 44 subspecies and various strains, varieties, andhybrids thereof. As used herein, the term “honeybee” refers to anymember of the Order Hymeoptera, Family Apidae, and includes, withoutlimitation, Apis andreniformis, Apis cerana, Apis dorsata, Apis florae,Apis koschevnikovi, Apis laboriosa, Apis mellifera, Apis nigrocincta,Apis rorea, subspecies thereof, and strains, varieties, and hybridsthereof.

In one embodiment, a honeybee repellent disclosed herein substantiallymimics the attractant chemosensory cues of a natural compound producedby a plant or plant part like a flower. In an aspect of this embodiment,a honeybee repellent disclosed herein substantially mimics a repellentchemosensory cue of 2-heptanone.

In aspects of this embodiment, a honeybee repellent disclosed herein hasa repellent chemosensory cue that is, e.g., about 75%, about 80%, about85%, about 90%, about 95%, about 97%, or about 100% that of therepellent chemosensory cue of 2-heptanone. In other aspects of thisembodiment, a honeybee repellent disclosed herein has a repellentchemosensory cue that is, e.g., at least 75%, at least 80%, at least85%, at least 90%, at least 95%, or at least 97% that of the repellentchemosensory cue of 2-heptanone. In other aspects of this embodiment, ahoneybee repellent disclosed herein has a repellent chemosensory cuethat is between, e.g., about 75% to about 97%, about 80% to about 97%,about 85% to about 97%, about 90% to about 97%, about 75% to about 100%,about 80% to about 100%, about 85% to about 100%, or about 90% to about100% that of the repellent chemosensory of 2-hepta none.

In an embodiment, a honeybee repellent disclosed herein has a repellentchemosensory cue that is, e.g., at least one-fold, at least two-fold, atleast three-fold, at least four fold, at least five-fold, at leastsix-fold, at least seven-fold, at least eight-fold, at least nine-fold,at least 10-fold, at least 20-fold, at least 30-fold, at least 40-fold,at least 50-fold, at least 60-fold, at least 70-fold, at least 80-fold,at least 90-fold, at least 100-fold, at least 125-fold, at least150-fold, at least 175-fold, or at least 200-fold that of the repellentchemosensory cue of 2-heptanone.

In an embodiment, a honeybee repellent disclosed herein has a honeybeerepellency activity. In aspects of this embodiment, presence of ahoneybee repellent repels honeybees by, e.g., at least 10%, at least15%, at least 20%, at least 25%, at least 30%, at least 35%, at least40%, at least 45%, at least 50%, at least 55%, at least 60%, at least65%, at least 70%, at least 75%, at least 80%, at least 85%, at least90%, or at least 95%, as compared to not having the honeybee repellentpresent. In other aspects of this embodiment, presence of a honeybeerepellent repels honeybees by, e.g., about 10% to about 100%, about 20%to about 100%, about 30% to about 100%, about 40% to about 100%, about50% to about 100%, about 60% to about 100%, about 70% to about 100%,about 80% to about 100%, about 10% to about 90%, about 20% to about 90%,about 30% to about 90%, about 40% to about 90%, about 50% to about 90%,about 60% to about 90%, about 70% to about 90%, about 10% to about 80%,about 20% to about 80%, about 30% to about 80%, about 40% to about 80%,about 50% to about 80%, or about 60% to about 80%, about 10% to about70%, about 20% to about 70%, about 30% to about 70%, about 40% to about70%, or about 50% to about 70%, as compared to not having the honeybeerepellent present.

In an embodiment, a honeybee repellent disclosed herein reduces ahoneybee interaction with a mammal, a plant, structure, and/or location.In aspects of this embodiment, a honeybee repellent reduces honeybeeinteraction with a mammal, plant, structure, and/or location by, e.g.,at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, atleast 35%, at least 40%, at least 45%, at least 50%, at least 55%, atleast 60%, at least 65%, at least 70%, at least 75%, at least 80%, atleast 85%, at least 90%, or at least 95%. In other aspects of thisembodiment, a honeybee repellent reduces honeybee interaction with amammal, a plant, structure, and/or location by, e.g., about 10% to about100%, about 20% to about 100%, about 30% to about 100%, about 40% toabout 100%, about 50% to about 100%, about 60% to about 100%, about 70%to about 100%, about 80% to about 100%, about 10% to about 90%, about20% to about 90%, about 30% to about 90%, about 40% to about 90%, about50% to about 90%, about 60% to about 90%, about 70% to about 90%, about10% to about 80%, about 20% to about 80%, about 30% to about 80%, about40% to about 80%, about 50% to about 80%, or about 60% to about 80%,about 10% to about 70%, about 20% to about 70%, about 30% to about 70%,about 40% to about 70%, or about 50% to about 70%.

In an embodiment, a honeybee repellent disclosed herein reduces anability of a honeybee to obtain a meal and/or nectar from a plant. Inaspects of this embodiment, a honeybee repellent reduces an ability of ahoneybee to obtain a meal from a plant by, e.g., at least 10%, at least15%, at least 20%, at least 25%, at least 30%, at least 35%, at least40%, at least 45%, at least 50%, at least 55%, at least 60%, at least65%, at least 70%, at least 75%, at least 80%, at least 85%, at least90%, or at least 95%. In other aspects of this embodiment, a honeybeerepellent reduces an ability of a honeybee to obtain a meal and/ornectar from a plant by, e.g., about 10% to about 100%, about 20% toabout 100%, about 30% to about 100%, about 40% to about 100%, about 50%to about 100%, about 60% to about 100%, about 70% to about 100%, about80% to about 100%, about 10% to about 90%, about 20% to about 90%, about30% to about 90%, about 40% to about 90%, about 50% to about 90%, about60% to about 90%, about 70% to about 90%, about 10% to about 80%, about20% to about 80%, about 30% to about 80%, about 40% to about 80%, about50% to about 80%, or about 60% to about 80%, about 10% to about 70%,about 20% to about 70%, about 30% to about 70%, about 40% to about 70%,or about 50% to about 70%.

A honeybee repellant disclosed herein may be more stable (or lessvolatile) than 2-heptanone. In aspects of this embodiment, a honeybeerepellant disclosed herein has a half-life of, e.g., about one day,about three days, about five days, about one week, about two weeks,about three weeks, about one month, about two months, or about threemonths. In other aspects of this embodiment, a honeybee repellantdisclosed herein has a half-life of, e.g., at least one day, at leastthree days, at least five days, at least one week, at least two weeks,at least three weeks, at least one month, at least two months, or atleast three months. In yet other aspects of this embodiment, a honeybeerepellant disclosed herein has a half-life of between, e.g., about oneday to about seven days, about three days to about seven days, aboutfive days to about seven days, about one week to about four weeks, abouttwo weeks to about four weeks, about three weeks to about four weeks,about one month to about four months, about two months to about fourmonths, or about three months to about four months.

A honeybee repellent may preferentially bind, without limitation, anodorant Binding Protein 2 (OBP2). OBP2, also known as ASP2, refers to asoluble, acidic protein of about 13-16 kDa that is expressed in sensorytissues of honeybees. This protein binds 2-heptanone and escorts thiscompound across the hydrophilic extracellular matrix to the cellsurface, where odorant receptors are located. Exemplary honeybee OBP2sinclude, without limitation, Apis mellifera OBP2 (SEQ ID NO: 1) and Apiscerana OBP2 (SEQ ID NO: 2). For a general review see, e.g., Dani, etal., Mapping the Expression of Soluble Olfactory Proteins in theHoneybee, J. Proteome Res. 9(4): 1822-1833 (2010); Pelosi, et al.,Soluble Proteins in Insect Chemical Communication, Cell. Mol. Life Sci.63(14): 1658-1676 (2006); Calvello, et al., Expression ofOdorant-Binding Proteins and Chemosensory Proteins in Some Hymenoptera,Insect Biochem. Mol. Biol. 35(4): 297-307 (2005), each of which ishereby incorporated by reference in its entirety.

A honeybee repellent disclosed herein may be characterized by it bindingaffinity. Binding affinity can be described by an equilibriumdissociation constant (KD), which is defined as the ratio Kd/Ka atequilibrium; where Ka is the association rate constant of the repellentcompound and kd is the dissociation rate constant of the repellentcompound. Binding affinity is determined by both the association and thedissociation and alone neither high association or low dissociation canensure high affinity. The association rate constant (Ka), or on-rateconstant (Kon), measures the number of binding events per unit time, orthe propensity of the repellent compound and the honeybee OBP toassociate reversibly into its repellent-OBP complex. The associationrate constant is expressed in M⁻¹ s⁻¹. The larger the association rateconstant, the more rapidly the repellent compound binds to its honeybeeOBP, or the higher the binding affinity between repellent compound andhoneybee OBP. The dissociation rate constant (Kd), or off-rate constant(Koff), measures the number of dissociation events per unit timepropensity of a repellent-OBP complex to separate (dissociate)reversibly into its component molecules, namely the repellent compoundand the honeybee OBP. The dissociation rate constant is expressed ins⁻¹. The smaller the dissociation rate constant, the more tightly boundthe repellent compound is to its honeybee OBP, or the higher the bindingaffinity between repellent compound and honeybee OBP. The equilibriumdissociation constant (KD) measures the rate at which new repellent-OBPcomplexes formed equals the rate at which repellent-OBP complexesdissociate at equilibrium. The equilibrium dissociation constant isexpressed in M, and is defined as Koff/Kon=[L]×[R]/[L+R], where [L] isthe molar concentration of the repellent compound, [R] is the molarconcentration of the honeybee OBP, and [L+R] is the molar concentrationof the repellent-OBP complex, where all concentrations are of suchcomponents when the system is at equilibrium. The smaller theequilibrium dissociation constant, the more tightly bound the repellentcompound is to its honeybee OBP, or the higher the binding affinitybetween repellent compound and honeybee OBP.

In an embodiment, a honeybee repellent disclosed herein has a bindingaffinity that is substantially the same as the binding affinity of thenatural ligand for that honeybee OBP. In aspects of this embodiment, ahoneybee repellent disclosed herein has a binding affinity for ahoneybee OBP that is, e.g., about 75%, about 80%, about 85%, about 90%,about 95%, about 97%, or about 100% that of the binding affinity of thenatural ligand for that honeybee OBP. In other aspects of thisembodiment, a honeybee repellent disclosed herein has a binding affinityfor a honeybee OBP that is, e.g., at least 75%, at least 80%, at least85%, at least 90%, at least 95%, or at least 97% that of the bindingaffinity of the natural ligand for that honeybee OBP. In other aspectsof this embodiment, a honeybee repellent disclosed herein has a bindingaffinity for a honeybee OBP that is between, e.g., about 75% to about97%, about 80% to about 97%, about 85% to about 97%, about 90% to about97%, about 75% to about 100%, about 80% to about 100%, about 85% toabout 100%, or about 90% to about 100% that of the binding affinity ofthe natural ligand for that honeybee OBP.

In an embodiment, the binding affinity of a honeybee repellent thatbinds to a honeybee OBP has a dissociation equilibrium constant that isgreater than the dissociation equilibrium constant of the natural ligandfor that honeybee OBP. In aspects of this embodiment, the bindingaffinity of a honeybee repellent that binds to a honeybee OBP has adissociation equilibrium constant that is greater than the dissociationequilibrium constant of the natural ligand for that honeybee OBP by,e.g., at least one-fold, at least two-fold, at least three-fold, atleast four fold, at least five-fold, at least six-fold, at leastseven-fold, at least eight-fold, at least nine-fold, at least 10-fold,at least 20-fold, at least 30-fold, at least 40-fold, at least 50-fold,at least 60-fold, at least 70-fold, at least 80-fold, at least 90-fold,at least 100-fold, at least 125-fold, at least 150-fold, at least175-fold, or at least 200-fold.

In another embodiment, a honeybee repellent disclosed herein binds to ahoneybee OBP with binding affinity having an association rate constantof, e.g., less than 1×10⁵ M⁻¹ s⁻¹, less than 1×10⁶ M⁻¹ s⁻¹, less than1×10⁷ M⁻¹ s⁻¹, or less than 1×10⁸ M⁻¹ s⁻¹. In another embodiment, ahoneybee repellent disclosed herein binds to a honeybee OBP with bindingaffinity having an association rate constant of, e.g., more than 1×10⁵M⁻¹ s⁻¹, more than 1×10⁶ M⁻¹ s⁻¹, more than 1×10⁷ M⁻¹ s⁻¹, or more than1×10⁸ M⁻¹ s⁻¹. In another embodiment, a honeybee repellent disclosedherein binds to a honeybee OBP with binding affinity having anassociation rate constant between 1×10⁵ M⁻¹ s⁻¹ to 1×10⁸ M⁻¹ s⁻¹, 1×10⁶M⁻¹ s⁻¹ to 1×10⁸ M⁻¹ s⁻¹, 1×10⁵ M⁻¹ s⁻¹ to 1×10⁷ M⁻¹ s⁻¹, or 1×10⁶ M⁻¹s⁻¹ to 1×10⁷ M⁻¹ s⁻¹.

In another embodiment, a honeybee repellent disclosed herein binds to ahoneybee OBP with binding affinity having a disassociation rate constantof less than 1×10⁻³ s⁻¹, less than 1×10⁻⁴ s⁻¹, or less than 1×10⁻⁵ s⁻¹.In another embodiment, a honeybee repellent disclosed herein binds to ahoneybee OBP with binding affinity having a disassociation rate constantof, e.g., less than 1.0×10⁻⁴ s⁻¹, less than 2.0×10⁻⁴ s⁻¹, less than3.0×10⁻⁴ s⁻¹, less than 4.0×10⁻⁴ s⁻¹, less than 5.0×10⁻⁴ s⁻¹, less than6.0×10⁻⁴ s⁻¹, less than 7.0×10⁻⁴ s⁻¹, less than 8.0×10⁻⁴ s⁻¹, or lessthan 9.0×10⁻⁴ s⁻¹. In another embodiment, a honeybee repellent disclosedherein binds to a honeybee OBP with binding affinity having adisassociation rate constant of, e.g., more than 1×10⁻³ s⁻¹, more than1×10⁻⁴ s⁻¹, or more than 1×10⁻⁵ s⁻¹. In another embodiment, a honeybeerepellent disclosed herein binds to a honeybee OBP with binding affinityhaving a disassociation rate constant of, e.g., more than 1.0×10⁻⁴ s⁻¹,more than 2.0×10⁻⁴ s⁻¹, more than 3.0×10⁻⁴ s⁻¹, more than 4.0×10⁻⁴ s⁻¹,more than 5.0×10⁻⁴ s⁻¹, more than 6.0×10⁻⁴ s⁻¹, more than 7.0×10⁻⁴ s⁻¹,more than 8.0×10⁻⁴ s⁻¹, or more than 9.0×10⁻⁴ s⁻¹.

In another embodiment, a honeybee repellent disclosed herein binds to ahoneybee OBP with binding affinity having an equilibrium disassociationconstant of less than 0.500 nM. In aspects of this embodiment, ahoneybee repellent disclosed herein binds to a honeybee OBP with bindingaffinity having an equilibrium disassociation constant of, e.g., lessthan 0.500 nM, less than 0.450 nM, less than 0.400 nM, less than 0.350nM, less than 0.300 nM, less than 0.250 nM, less than 0.200 nM, lessthan 0.150 nM, less than 0.100 nM, or less than 0.050 nM. In anotherembodiment, a honeybee repellent disclosed herein binds to a honeybeeOBP with binding affinity having an equilibrium disassociation constantof more than 0.500 nM. In aspects of this embodiment, a honeybeerepellent disclosed herein binds to a honeybee OBP with binding affinityhaving an equilibrium disassociation constant of, e.g., more than 0.500nM, more than 0.450 nM, more than 0.400 nM, more than 0.350 nM, morethan 0.300 nM, more than 0.250 nM, more than 0.200 nM, more than 0.150nM, more than 0.100 nM, or more than 0.050 nM.

In another embodiment, a honeybee repellent disclosed herein has abinding affinity that is substantially the same as the binding affinityof 2-heptanone for that honeybee OBP. In aspects of this embodiment, ahoneybee repellent disclosed herein has a binding affinity for ahoneybee OBP that is, e.g., about 75%, about 80%, about 85%, about 90%,about 95%, about 97%, or about 100% that of the binding affinity of2-heptanone for that honeybee OBP. In other aspects of this embodiment,a honeybee repellent disclosed herein has a binding affinity for ahoneybee OBP that is, e.g., at least 75%, at least 80%, at least 85%, atleast 90%, at least 95%, or at least 97% that of the binding affinity of2-heptanone for that honeybee OBP. In other aspects of this embodiment,a honeybee repellent disclosed herein has a binding affinity for ahoneybee OBP that is between, e.g., about 75% to about 97%, about 80% toabout 97%, about 85% to about 97%, about 90% to about 97%, about 75% toabout 100%, about 80% to about 100%, about 85% to about 100%, or about90% to about 100% that of the binding affinity of (R)-(+)-Limonene forthat honeybee OBP.

In an embodiment, the binding affinity of a honeybee repellent thatbinds to a honeybee OBP has a dissociation equilibrium constant that isgreater than the dissociation equilibrium constant of 2-heptanone forthat honeybee OBP by, e.g., at least one-fold, at least two-fold, atleast three-fold, at least four fold, at least five-fold, at leastsix-fold, at least seven-fold, at least eight-fold, at least nine-fold,at least 10-fold, at least 20-fold, at least 30-fold, at least 40-fold,at least 50-fold, at least 60-fold, at least 70-fold, at least 80-fold,at least 90-fold, at least 100-fold, at least 125-fold, at least150-fold, at least 175-fold, or at least 200-fold.

For convenience, the term “molecular weight” is used with respect to amoiety or part of a molecule to indicate the sum of the atomic masses ofthe atoms in the moiety or part of a molecule, even though it may not bea complete molecule.

As used herein, the term “acid anhydride” group refers to a moleculewith two acyl groups attached to the same oxygen, and general formula(RCO)₂O. As used herein, the term “acetyl” group refers to thefunctional group —C(═O)CH₃. As used herein, the term “acyl” refers to afunctional group comprising a carbonyl attached to an alkenyl, alkyl,aryl, cycloalkyl, heteroaryl, heterocycle, or any other moiety were theatom attached to the carbonyl is carbon. Examples of acyl groupsinclude, without limitation, formyl, alkanoyl and aroyl. As used herein,the term “acylamino” refers to a functional group comprising an acylgroup attached to the parent moiety through an amino group. Examples ofacylamino groups include, without limitation, acetylamino (CH₃C(═O)NH—).As used herein, the term “acyl halide” refers to the functional grouphaloformyl (COX, with X being a halogen). As used herein, the term“alcohol” refers to a molecule comprising a hydroxyl group (—OH), andhaving the general formula ROH, wherein R is an organic moiety or group.As used herein, the term “aldehyde” refers to a molecule comprising acarbonyl group [—C(═O)H], and having the general formula RCHO, wherein Ris an organic moiety or group.

As used herein, the term “alkene”, “olefin”, or “olefine” refers to astraight-chain or branched-chain hydrocarbon containing from 2 to 20carbon atoms and having one or more double bonds and not having anycyclic structure. An alkene with only one double bond has the generalformula CnH2n. An alkene with two carbon-carbon double bonds is called adiene, with three carbon-carbon double bonds is called a triene, andwith four carbon-carbon double bonds is called a tetraene. An alkene maybe optionally substituted as defined herein. Examples of alkenesinclude, without limitation, ethene, propene, butene, pentene, hexene,heptene, octene, nonene, decene, undecene, dodecene, tridecene,tetradecene, pentadecene, hexadecene, heptadecene, octadecene,nonadecene, eicosene, and the like.

As used herein, the term “alkenyl” refers to a functional group ormoiety comprising a straight-chain or branched-chain hydrocarboncontaining from 2 to 20 carbon atoms and having one or morecarbon-carbon double bonds and not having any cyclic structure includingstraight-chain or branched-chain hydrocarbon containing 2-6 carbonatoms, 3-6 carbon atoms, 3-7 carbon atoms, 4-7 carbon atoms, 4-8 carbonatoms, and 5-10 carbon atoms. An alkenyl group may be optionallysubstituted as defined herein. As used herein, “lower alkenyl” refers toalkenyl moieties having from 2 to about 6 carbon atoms. Examples ofalkenyl groups include, without limitation, ethenyl, propenyl,2-methylpropenyl, butenyl, 1,4-butadienyl, pentenyl, hexenyl, heptenyl,octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl,tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl,nonadecenyl, and eicosenyl. As used herein, the term “alkylene” refersto a saturated aliphatic functional group or moiety derived from astraight or branched chain saturated hydrocarbon attached at two or morepositions, such as methylene (—C₂—). An alkylene is a divalenthydrocarbyl radical, i.e., the alkylene moiety is attached to the otherparts of the molecule at two distinct positions. Unless otherwisespecified, the term “alkyl” may include “alkylene” groups.

As used herein, either alone or in combination, the term “alkoxy” refersto a functional group comprising an alkyl ether group. Examples ofalkoxys include, without limitation, methoxy, ethoxy, n-propoxy,isopropoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, and the like.

As used herein the term “alkyl” refers to a functional group or moietycomprising a straight-chain or branched-chain hydrocarbon containingfrom 1 to 35 carbon atoms linked exclusively by single bonds and nothaving any cyclic structure including straight-chain or branched-chainhydrocarbon containing 1 to 6 carbon atoms, 7 carbon atoms, 2-6 carbonatoms, 3-6 carbon atoms, 4-7 carbon atoms, 5-10 carbon atoms, 5-9 carbonatoms, and 5-8 carbon atoms. As used herein, “lower alkyl” refers toalkyl moieties having from 1 to about 6 carbon atoms. An alkyl group maybe optionally substituted as defined herein. Examples of alkyl groupsincludes, without limitation, methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, hexyl,heptyl, octyl, noyl, decyl, undecyl, dodecyl tridecyl, tetradecyl,pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, and eicosyl. Insome embodiments, alkyl may include C₁₋₁₀ linear alkyl, such as, e.g.,methyl (—CH₃), ethyl (—CH₂CH₃), n-propyl (—CH₂CH₂CH₃), n-butyl(—CH₂CH₂CH₂CH₃), n-pentyl (—CH₂CH₂CH₂CH₂CH₃), n-hexyl(—CH₂CH₂CH₂CH₂CH₂CH₃). In some embodiments, alkyl may include C₃₋₁₀branched alkyl, such as, e.g., C₃H₇ (e.g. iso-propyl), C₄H₉ (e.g.branched butyl isomers), C₅H₁₁ (e.g. branched pentyl isomers), C₆H₁₃(e.g. branched hexyl isomers), and C₇H₁₅ (e.g. heptyl isomers).

As used herein, the term “alkylamino” refers to a functional groupcomprising a saturated straight or branched alkyl substituted by one ormore amino groups. Examples of alkylamino groups includes, withoutlimitation methylamino and tert-butylamino. As used herein, the term“aminoalkyl” refers to a functional group comprising an alkyl groupattached to the parent molecular moiety through an amino group. Analkylamino group may be a mono- or dialkylated forming group such as,e.g., N-methylamino, N-ethylamino, N,N-dimethylamino,N,N-ethylmethylamino and the like. As used herein, the term“alkylcarbonyl” or “alkanoyl” refers to a functional group comprising analkyl group attached to the parent molecular moiety through a carbonylgroup. Examples of alkylcarbonyl groups include, without limitation,methylcarbonyl, ethylcarbonyl, and the like. As used herein, the term“alkylidene” refers to a functional group comprising an alkenyl group inwhich one carbon atom of the carbon-carbon double bond belongs to themoiety to which the alkenyl group is attached. As used herein, the term“alkylthio” refers to a saturated straight or branched alkyl chainsubstituted by one or more thiol groups. Examples of alkyl groupsincludes, without limitation methylthio, ethylthio, n-propylthio,isopropylthio, n-butylthio, iso-butylthio, sec-butylthio, andtert-butylthio.

As used herein, the term “alkynyl” refers to a functional group ormoiety comprising a straight-chain or branched-chain hydrocarboncontaining from 2 to 20 carbon atoms and having one or morecarbon-carbon triple bonds and not having any cyclic structure includingstraight-chain or branched-chain hydrocarbon containing 2-6 carbonatoms, 3-6 carbon atoms, 3-7 carbon atoms, 4-7 carbon atoms, 4-8 carbonatoms, and 5-10 carbon atoms. As used herein, “lower alkenyl” refers toalkenyl moieties having from 2 to about 6 carbon atoms. An alkynyl groupmay be optionally substituted as defined herein. Examples of alkynylgroups include, without limitation, ethynyl, propynyl, hydroxypropynyl,butynyl, butyn-1-yl, butyn-2-yl, 3-methylbutyn-1-yl, pentynyl,pentyn-1-yl, hexynyl, hexyn-2-yl, heptynyl, octynyl, nonynyl, decynyl,undecynyl, dodecynyl, tridecynyl, tetradecynyl, pentadecynyl,hexadecynyl, heptadecynyl, octadecynyl, nonadecynyl, and eicosynyl. Asused herein, the term “alkynylene” refers to a carbon-carbon triple bondattached at two positions such as ethynylene (—C:::C—, —C≡C—). Unlessotherwise specified, the term “alkynyl” may include “alkynylene” groups.

As used herein, the term “aryl” or “aryl hydrocarbon” refers to afunctional group or moiety comprising an aromatic hydrocarbon with aconjugated cyclic molecular ring structure of 3 to 12 carbon atomsincluding a conjugated cyclic molecular ring structure of 4 carbonatoms, 5 carbon atoms, 6 carbon atoms, 7 carbon atoms, 4-6 carbon atoms,4-5 carbon atoms, 5-6 carbon atoms, and 4-7 carbon atoms. As usedherein, “lower aryl” refers to aryl moieties having from 3 to about 6carbon atoms including, without limitation, phenyl and naphthyl. An arylgroup may be optionally substituted as defined herein. An aryl group canbe monocyclic, bicyclic or polycyclic, and may optionally include one tothree additional ring structures, such as, e.g., a cycloalkyl, acycloalkenyl, a heterocycloalkyl, a heterocycloalkenyl, or a heteroaryl.The term “aryl” includes, without limitation, phenyl (benzenyl),thiophenyl, indolyl, naphthyl, totyl, xylyl, anthracenyl, phenanthryl,azulenyl, biphenyl, naphthalenyl, 1-mMethylnaphthalenyl, acenaphthenyl,acenaphthylenyl, anthracenyl, fluorenyl, phenalenyl, phenanthrenyl,benzo[a]anthracenyl, benzo[c]phenanthrenyl, chrysenyl, fluoranthenyl,pyrenyl, tetracenyl (naphthacenyl), triphenylenyl, anthanthrenyl,benzopyrenyl, benzo[a]pyrenyl, benzo[e]fluoranthenyl,benzo[ghi]perylenyl, benzo[j]fluoranthenyl, benzo[k]fluoranthenyl,corannulenyl, coronenyl, dicoronylenyl, helicenyl, heptacenyl,hexacenyl, ovalenyl, pentacenyl, picenyl, perylenyl, andtetraphenylenyl.

As used herein, the term “arylalkenyl” or “aralkenyl” refers to afunctional group comprising an aryl group attached to the parentmolecular moiety through an alkenyl group. As used herein, the term“arylalkoxy” or “aralkoxy” refers to a functional group comprising anaryl group attached to the parent molecular moiety through an alkoxygroup. As used herein, the term “arylalkyl” or “aralkyl,” refers to afunctional group comprising an aryl group attached to the parentmolecular moiety through an alkyl group. As used herein, the term“arylalkynyl” or “aralkynyl” refers to a functional group comprising anaryl group attached to the parent molecular moiety through an alkynylgroup. As used herein, the term “arylalkanoyl” or “aralkanoyl” or“aroyl” refers to a functional group comprising an acyl group derivedfrom an aryl-substituted alkanecarboxylic acid such as, e.g., benzoyl,napthoyl, phenylacetyl, 3-phenylpropionyl (hydrocinnamoyl),4-phenylbutyryl, (2-naphthyl)acetyl, 4-chlorohydrocinnamoyl, and thelike. As used herein, the term “aryloxy” refers to a functional groupcomprising an aryl group attached to the parent molecular moiety throughan oxy group.

As used herein, the term “cycloalkyl”, “carbocyclicalkyl”, and“carbocyclealkyl” refers to a functional group or moiety comprising anon-aromatic hydrocarbon with a non-conjugated cyclic molecular ringstructure of 3 to 12 carbon atoms linked exclusively with carbon-carbonsingle bonds in the carbon ring structure including a non-conjugatedcyclic molecular ring structure of 4 carbon atoms, 5 carbon atoms, 6carbon atoms, 3-8 carbon atoms, 3-7 carbon atoms, 4-7 carbon atoms, 4-6carbon atoms, 4-5 carbon atoms, and 5-6 carbon atoms. A cycloalkyl groupmay be optionally substituted as defined herein. As used herein, “lowercycloalkyl” refers to cycloalkyl moieties having from 3 to about 6carbon atoms. A cycloalkyl group can be monocyclic, bicyclic orpolycyclic, and may optionally include one to three additional ringstructures, such as, e.g., an aryl, a heteroaryl, a cycloalkenyl, aheterocycloalkyl, or a heterocycloalkenyl. In some embodiments, acycloalkyl may include C₃₋₁₀ cycloalkyl, such as, e.g., C₃H₅ (e.g.cyclopropyl), C₄H₇ (e.g. cyclobutyl isomers like cyclobutyl andmethylcyclopropyl), C₅H₉ (e.g. cyclopentyl isomers like cyclopentyl,methylcyclobutyl, and dimethylcyclopropyl) C₆H₁₁ (e.g. cyclohexylisomers), and C₇H₁₃ (e.g. cycloheptyl isomers).

As used herein, the term “diene” refers to a functional group comprisinga straight-chain or branched-chain hydrocarbon with two carbon-carbondouble bonds and having the general formula of C_(n)H_(2n-2). A dienecan be unconjugated, conjugated or cumulative. Examples of diene groupsinclude, without limitation, allene (propan-1,2-diene), 1,3-butadiene,chloroprene, hexachlorobutadiene, isoprene (2-methyl-1,3-butadiene),isotoluene, myrcenol, and piperylene. As used herein, the term“cyclodiene” refers to a functional group comprising a substituted orunsubstituted non-aromatic hydrocarbon with a cyclic molecular ringstructure of 3 to 12 carbon atoms and having two carbon-carbon doublebonds in the carbon ring structure. A cyclodiene can be unconjugated,conjugated or cumulative. Examples of cyclodiene groups include, withoutlimitation, cyclopentadiene, 1,5-cyclooctadiene,hexachlorocyclopentadiene, and methylcyclopentadiene. As used herein,the term “enone” refers to a functional group comprising an alkene and akeyone, and having the general formula RC(O)C(R′)CR″R′″, wherein R, R′,R″, and R′″ are an organic moiety or group. As used herein, the term“ester” refers to a molecule comprising a carboxyl group or derivativethereof, and having the general formula RC(O)OR′, wherein R and R′ arean organic moeity or group. As used herein, the term “ether” refers to amolecule comprising an oxy group, and having the general formula ROR′,wherein R and R′ are an organic moeity or group.

As used herein, the term “halogen”, “halo” or “halide” refers to afunctional group or moiety comprising one or more halogens attached toan element or radical, like a monohalo, dihalo, or trihalo, such as F,Cl, Br, I, F₂, Cl₂, Br₂, I₂, F₃, Cl₃, Br₃, I₃, etc. Examples of a halidegroup includes, without limitation, fluoride (F), chloride (Cl), bromide(Br), iodide (I), astatide (At), or ununseptide (Uus) and may also bereferred to as fluoro, chloro, bromo, iodo, astato, or ununsepto. Asused herein, the term “haloalkenyl” refers to a functional groupcomprising an alkenyl group where one of more of the hydrogen atoms isreplaced by halogen atoms on the unsaturated carbon atoms. As usedherein, the term “haloalkoxy” refers to a functional group comprising ahaloalkyl group attached to the parent molecular moiety through anoxygen atom. As used herein, the term “haloalkyl” refers to a functionalgroup comprising an alkyl group where one of more of the hydrogen atomsis replaced by halogen atoms. A haloalkyl can be a monohaloalkyl, adihaloalkyl or a polyhaloalkyl. A monohaloalkyl group may have an iodo,bromo, chloro or fluoro atom within the group. A dihalo andpolyhaloalkyl group may have two or more of the same halo atoms or acombination of different halo groups. Examples of haloalkyl groupsinclude, without limitation, fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,pentafluoroethyl, heptafluoropropyl, difluorochloromethyl,dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl anddichloropropyl. As used herein, the term “haloalkylene” refers to afunctional group comprising a haloalkyl group attached at two or morepositions. Examples of a haloalkylene group include, without limitation,fluoromethylene (—CFH—), difluoromethylene (—CF₂—), chloromethylene(—CHCl—) and the like.

As used herein, the term “heteroalkenyl” refers to a functional group ormoiety comprising a straight-chain or branched-chain hydrocarboncontaining from 2 to 20 atoms and having one or more carbon-carbondouble bonds and not having any cyclic structure, where at least oneatom in the ring structure is a carbon and at least one atom in the ringstructure is N, O, S, or any combination thereof.

For example, a heteroalkenyl includes a straight-chain or branched-chainhydrocarbon containing at least one N O, S, or any combination thereofand containing 2-6 carbon atoms, 3-6 carbon atoms, 3-7 carbon atoms, 4-8carbon atoms, and 5-10 carbon atoms. The non-carbon atoms can be at anyinterior position of the heteroalkenyl group, and up to two non-carbonatoms may be consecutive, such as, e.g., —CH₂—NH—OCH₃. In addition, thenon-carbon atoms may optionally be oxidized and the nitrogen mayoptionally be quaternized. As used herein, “lower heteroalkenyl” refersto heteroalkenyl moieties having from 2 to about 6 carbon atoms. Aheteroalkenyl group may be optionally substituted as defined herein.

As used herein, the term “heteroalkyl” or “heterocyclic” refers to afunctional group or moiety comprising a straight-chain or branched-chainhydrocarbon containing from 1 to 20 atoms linked exclusively by singlebonds, and not having any cyclic structure, where at least one atom inthe chain is a carbon and at least one atom in the chain is N O, S, orany combination thereof. For example, a heteroalkyl includes astraight-chain or branched-chain hydrocarbon containing at least one NO, S, or any combination thereof and 1 to 6 carbon atoms, 2-6 carbonatoms, 3-6 carbon atoms, 4-7 carbon atoms, 5-10 carbon atoms, 5-9 carbonatoms, and 5-8 carbon atoms. The non-carbon atoms can be at any interiorposition of the heteroalkyl group, and up to two non-carbon atoms may beconsecutive, such as, e.g., —CH₂—NH—OCH₃. In addition, the non-carbonatoms may optionally be oxidized and the nitrogen may optionally bequaternized. As used herein, “lower heteroalkyl” refers to heteroalkylmoieties having from 2 to about 6 carbon atoms. A heteroalkyl group maybe optionally substituted as defined herein.

As used herein, the term “heteroaryl” refers to a functional group ormoiety comprising an aromatic hydrocarbon with a conjugated cyclicmolecular ring structure of 3 to 12 atoms, where at least one atom inthe ring structure is a carbon and at least one atom in the ringstructure is N, O, S, or any combination thereof including a conjugatedcyclic molecular ring structure of 3 carbon atoms, 4 carbon atoms, 5carbon atoms, 6 carbon atoms, 7 carbon atoms, 3-6 carbon atoms, 4-6carbon atoms, 4-5 carbon atoms, 5-6 carbon atoms, and 4-7 carbon atoms.As used herein, “lower heteroaryl” refers to heteroaryl moieties havingfrom 3 to about 6 carbon atoms. A heteroaryl group may be optionallysubstituted as defined herein. A heteroaryl group can be monocyclic,bicyclic or polycyclic, and may optionally include one to threeadditional ring structures, such as, e.g., an aryl, a cycloalkyl, acycloalkenyl, a heterocycloalkyl, or a heterocycloalkenyl. Examples ofheteroaryl groups include, without limitation, acridinyl, benzidolyl,benzimidazolyl, benzisoxazolyl, benzodioxinyl, dihydrobenzodioxinyl,benzodioxolyl, 1,3-benzodioxolyl, benzofuryl, benzoisoxazolyl,benzopyranyl, benzothiophenyl, benzo[c]thiophenyl, benzotriazolyl,benzoxadiazolyl, benzoxazolyl, benzothiadiazolyl, benzothiazolyl,benzothienyl, carbazolyl, chromonyl, cinnolinyl, dihydrocinnolinyl,coumarinyl, dibenzofuranyl, furopyridinyl, furyl, indolizinyl, indolyl,dihydroindolyl, imidazolyl, indazolyl, isobenzofuryl, isoindolyl,isoindolinyl, dihydroisoindolyl, isoquinolyl, dihydroisoquinolinyl,isoxazolyl, isothiazolyl, oxazolyl, oxadiazolyl, phenanthrolinyl,phenanthridinyl, purinyl, pyranyl, pyrazinyl, pyrazolyl, pyridyl,pyrimidinyl, pyridazinyl, pyrrolinyl, pyrrolyl, pyrrolopyridinyl,quinolyl, quinoxalinyl, quinazolinyl, tetrahydroquinolinyl,tetrazolopyridazinyl, tetrahydroisoquinolinyl, thiophenyl, thiazolyl,thiadiazolyl, thienopyridinyl, thienyl, thiophenyl, triazolyl,xanthenyl, and the like.

As used herein, the term “heterocycloalkenyl” refers to a functionalgroup or moiety comprising a non-aromatic hydrocarbon with anon-conjugated cyclic molecular ring structure of 3 to 12 atoms havingat least one double bond, where at least one atom in the ring structureis a carbon and at least one atom in the ring structure is N, O, S, orany combination thereof including a conjugated cyclic molecular ringstructure of 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, 6 carbonatoms, 7 carbon atoms, 3-6 carbon atoms, 4-6 carbon atoms, 4-5 carbonatoms, 5-6 carbon atoms, and 4-7 carbon atoms. As used herein, “lowerheterocycloalkenyl” refers to heterocycloalkenyl moieties having from 3to about 6 carbon atoms. A heterocycloalkenyl group may be optionallysubstituted as defined herein. A heterocycloalkenyl group can bemonocyclic, bicyclic or polycyclic, and may optionally include one tothree additional ring structures, such as, e.g., an aryl, a heteroaryl,a cycloalkyl, a heterocycloalkyl, or a cycloalkenyl.

As used herein, the term “heterocycloalkyl”, “heterocyclicalkyl”, and“heterocyclealkyl” refers to a functional group comprising anon-aromatic hydrocarbon with a non-conjugated cyclic molecular ringstructure of 3 to 12 atoms linked exclusively with single bonds in thering structure, where at least one atom in the ring structure is acarbon and at least one atom in the ring structure is N, O, S, or anycombination thereof. As used herein, “lower heterocycloalkyl” refers toheterocycloalkyl moieties having from 3 to about 6 carbon atoms,including, without limitation, pyrrolidinyl, imidazolidinyl,pyrazolidinyl, piperidinyl, piperazinyl, and morpholinyl. Aheterocycloalkyl group may be optionally substituted as defined herein.A heterocycloalkyl group can be monocyclic, bicyclic or polycyclic, andmay optionally include one to three additional ring structures, such as,e.g., an aryl, a heteroaryl a cycloalkyl, a cycloalkenyl, or aheterocycloalkenyl. A heterocycle group may be optionally substitutedunless specifically prohibited. Examples of such heterocycloalkyl groupsinclude, without limitation, ariridinyl, azirinyl, diazirinyl, oxiranyl,oxirenyl, dioxiranyl, thiiranyl, thiirenyl, azetidinyl, azetyl,diazetidinyl, oxetanyl, oxetyl, dioxetanyl, dioxetenyl, thietanyl,thietyl, dithietanyl, dithietyl, pyrrolidinyl, pyrrolinyl, pyrrolyl,furanyl, dihydrofuranyl, tetrahydrofuranyl, tetrahydrothiophenyl,dihydrothiophenyl, thiophenyl, imidazolidinyl, pyrazolidinyl,imidazolyl, imidazolinyl, pyrazolyl, pyrazolinyl, oxazolidinyl,isoxazolidinyl, oxazolyl, oxazolinyl, isoxazolyl, isoxazolinyl,thiazolidinyl, isothiazolidinyl, thiazolyl, thiazolinyl, isothiazolyl,isothiazolinyl, dioxolanyl, 1,3-dioxanyl, 1,4-dioxanyl, dioxolanyl,1,3-dioxolanyl, oxathiolanyl, dithiolanyl, triazolyl, dithiazolyl,furazanyl, oxadiazolyl, thiadiazolyl, tetrazolyl, piperidinyl,tetrahydropyridinyl, pyridinyl, dihydropyridinyl,dihydro[1,3]oxazolo[4,5-b]pyridinyl, pyranyl, tetrahydropyranyl,thianyl, thiopyranyl, piperazinyl, diazinyl, morpholinyl,thiomorpholinyl, oxazinyl, thiazinyl, dithianyl, dioxanyl, dioxinyl,triazinyl, trioxanyl, tetrazinyl, azepanyl, azepinyl, oxepanyl,oxepinyl, thiepanyl, thiepinyl, diazepinyl, thiazepinyl, azocanyl,azocinyl, oxecanyl, and thiocanyl.

As used herein, the term “hydroxyalkyl” refers to a functional groupcomprising a hydroxy group attached to the parent molecular moietythrough an alkyl group. As used herein, the term “oxyalkyl” refers to afunctional group comprising an alkyl group attached to the parentmolecular moiety through an oxy group. As used herein, the term“oxoalkyl” refers to a functional group comprising an alkyl groupattached to the parent molecular moiety through an oxo group. As usedherein, the term “oxime” refers to a molecule comprising an imine group(C═N) and having the general formula RR′C═NOH, wherein R and R′ are anorganic moeity or group. An oxime where R or R′ is a hydrogen is oximineis called an aldoxime, whereas when both R and R′ are not hydrogens, theoxime is called a ketooxime. As used herein, the term “perhaloalkoxy”refers to a functional group comprising an alkoxy group where all of thehydrogen atoms are replaced by halogen atoms. As used herein, the term“perhaloalkyl” refers to a functional group comprising an alkyl groupwhere all of the hydrogen atoms are replaced by halogen atoms. As usedherein, the term “thioalkyl” refers to a functional group comprising analkyl group attached to the parent molecular moiety through a thiogroup.

Unless otherwise indicated, when a compound or chemical structuralfeature, such as functional group or moiety, is referred to as being“optionally substituted,” it includes a feature that has no substituents(i.e. be unsubstituted), or a feature that is “substituted,” meaningthat the feature has one or more substituents. The term “substituent”has the broadest meaning known to one of ordinary skill in the art, andincludes a functional group or moiety that replaces one or more hydrogenatoms attached to a parent compound or structural feature. Thus, anoptionally substituted group may be unsubstituted (e.g., —CH₂CH₃), fullysubstituted (e.g., —CF₂CF₃), monosubstituted (e.g., —CH₂CH₂F) orsubstituted at a level anywhere in between fully substituted andmonosubstituted (e.g., —CH₂CH₂F, —CHFCH₂F, —CH₂ CHF₂, —CHFCHF₂). In someembodiments, the substituent may be an ordinary organic moiety known inthe art, which may have a molecular weight (e.g. the sum of the atomicmasses of the atoms of the substituent) of 15 g/mol to 50 g/mol, 15g/mol to 100 g/mol, 15 g/mol to 150 g/mol, 15 g/mol to 200 g/mol, 15g/mol to 300 g/mol, or 15 g/mol to 500 g/mol. In some embodiments, thesubstituent comprises: 0-30, 0-20, 0-10, or 0-5 carbon atoms; and 0-30,0-20, 0-10, or 0-5 heteroatoms independently selected from: N, O, S, Si,F, Cl, Br, or I; provided that the substituent comprises at least oneatom selected from: C, N, O, S, Si, F, Cl, Br, or I. Examples ofsubstituents include, but are not limited to acid anhydride, acetyl,acyl, acylamino, acyl halide, acyloxy, alkenyl, alkoxy, alkyl,alkylamino, alkylcarbonyl, alkylcarboxylate, alkyloxy, alkyloxo,alkylthio, alkynyl, amide [—C(═O)NH₂], amidine (—C(═NH)NH₂), amido(—C(═O)—N), amino (—NH₂—), aminoalkyl, aryl, arylamino, arylalkenyl,arylalkoxy, arylalkyl, arylalkynyl, arylalkanoyl, aryloxy, arylthio,azide (—N═N═N), azo (—N═N—), benzo (C₆H₄), carbamyl [—NHC(═O)O-],carbonyl [—C(═O)H or the corresponding “carbonylate” anion —C(═O)—],carboxyl [—C(═O)OH or the corresponding “carboxylate” anion —C(═O)O-],carboxamide (—C(═O)NH₂), carboxamidine (—C(═NH)NH₂), cyanate [—(OC≡N)—],cyano (—C≡N), cycloalkenyl, cycloalkyl, diene, cyclodiene, disulfanyl(—S═S—), enone, halide, halo, haloalkenyl, haloalkoxyl, haloalkyl,halogen, heteroalkenyl, heteroalkyl, heteroalkynyl, heteroaryl,heterocycloalkenyl, heterocycloalkyl, hydrazinyl (—NHNH₂—), hydrazine(—C═N—), hydrogen (H), hydroperoxide (—OOH), hydroxyl (—OH),hydroxyalkyl, imidate (C═N—), imide [—C(═O)NC(═O)—], imine (—C═NH—),imino (═NH—), iminohydroxy (═N(OH) and its corresponding anion ═N—O—),isocyanato (—NCO), isothiocyanato (—NCS), isocyanate (—N═C═O),isocyanide (—NEC), isothiocyanate (—N═C═S), keto (—C═O), mercaptyl(—S—), nitrile (—C≡N), nitrite (—NO₂—), nitroso (—N═O), nitro (—NO₂),nitrate (—NO₃—), oxo (═O), oxy (—O—), oxoalkyl, oxyalkyl, oxime,perhaloalkoxy, perhaloalkyl, peroxy (—OO—), silyl, sulfanyl (—S—),sulfenyl, sulfhydryl (—SH), sulfinyl[-S(O)—], sulfonyl[-S(O)₂—], sulfyl[—S(O)₃—], sulfonamide [—S(O)₂N—], thioalkyl, thiocarbonyl [—C(S)H],thiocarbamyl (—OC(S)N—), thiocyanate [—(SC≡N)⁻], isothiocyanate (N═C═S),thiocyanato (CNS), thioketo (—C═S), thiol (S), trihalomethanesulfonyl(X₃CS(O)₂—, with X being a halogen), trihalomethanesulfonamido(X₃CS(O)₂N—, with X being a halogen), trihalomethoxy (X₃CO—, with Xbeing a halogen), and all lower forms therein.

In some embodiments, any substituent may independently be C₁₋₅ alkyl,such as CH₃, C₂H₅, C₃H₇, C₄H₉, O₅H₁₁, cyclopropyl, cyclobutyl,cyclopentyl, etc.; C₁₋₄ —O-alkyl, such as —O—CH₃, —O—C₂H₅, —O—C₃H₇,—O-cyclopropyl, etc.; C₂₋₄ alkenyl, such as —CH₂—CH═CH₂; —O—CH₂CH═CH₂;ester functional groups, such as C₁₋₄ —CO₂-alkyl (e.g. —CO₂CH₃,—CO₂O₂H₅, —CO₂O₃H₇, etc.), C₁₋₄ acyloxy, (e.g. —OCOCH₃, —OCOC₂H₅,—OCOC₃H₇, etc.), —CO₂—CF₃, etc.; halo, like a monohalo, dihalo, ortrihalo, such as F, Cl, Br, I, F₂, C₁₂, Br₂, I₂, F₃, C₁₃, Br₃, I₃, etc.;NO₂; ═O; ═S; —OH; amino, such as C₁₋₁₂ amino including NH₂, NHCH₃,N(CH₃)₂, N(C₂H₅)₂, NH(C₃H₇), etc.; amide functional groups, such asC₁₋₁₂ amide groups including —CONH₂, CONH(CH₃), CON(CH₃)₂, CON(C₂H₅)₂,—NCOC₄H₉, etc.; —C═N—OH; —C═N—CH₃; C₁₋₄ acyl, such as COH, COCH₃,COC₂H₅, etc.; COCF₃; —NCOC₄H₉; or two substituents may together be—CH₂—, —C₂H₄—, —C₃H₆—, —O—CH₂—, —O—C₂H₄—, —O—C₃H₆—, —CH₂—O—, —C₂H₄—O—,—C₃H₆—O—, —O—CH₂—O—, —O—C₂H₄—O—, or —O—C₃H₆—O—.

Unless otherwise indicated, any reference to a compound herein bystructure, name, or any other means, includes pharmaceuticallyacceptable salts, such as sodium, potassium, and ammonium salts;alternate solid forms, such as polymorphs, solvates, hydrates, etc.;tautomers; or any other chemical species that may rapidly convert to acompound described herein under conditions in which the compounds areused as described herein.

Thus, in one embodiment, a honeybee repellant may be a compound offormula I:

wherein: X¹ and X² are each independently N, O or S; L¹ and L² are eachindependently C₀, C₁-C₆ alkyl, C₁-C₆ alkylene, C₂-C₆ alkenyl, C₂-C₆alkynyl; Ar¹ and Ar² are each independently aryl, heteroaryl,substituted aryl, or substituted heteroaryl; R¹ is H, OH, OOH, O, OO,C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH,C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N, SCN, CNS, (N)C(S), NH, NH₂,NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH,S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl, halide, haloalkenyl,haloalkoxyl, haloalkyl, halogen, trihalomethanesulfonyl,trihalomethanesulfonamido, trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; and n is 1or 2.

In aspects of this embodiment, a honeybee repellant may be a compound offormula Ia:

wherein: X¹ and X² are each independently N, O or S; L¹ and L² are eachindependently C₀, C₁-C₆ alkyl, C₁-C₆ alkylene, C₂-C₆ alkenyl, C₂-C₆alkynyl; R¹, R² and R³ are each independently H, OH, OOH, O, OO, C(O),C(O)H, C(O)OH, OC(O)O, C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N,OCN, NHC(O)O, CS, C(S)H, OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN,NN, N(OH), NC, NCO, (N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O),S(O)₂, S(O)₃, S(O)₂N, aminoalkyl, halide, haloalkenyl, haloalkoxyl,haloalkyl, halogen, trihalomethanesulfonyl, trihalomethanesulfonamido,trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl,CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; and n is 1 or 2.

In other aspects of this embodiment, a honeybee repellant may be acompound of formula Ib:

wherein: X¹ and X² are each independently N, O or S; L¹ is C₀, C₁-C₆alkyl, C₁-C₆ alkylene, C₂-C₆ alkenyl, C₂-C₆ alkynyl; Ar¹ and Ar² areeach independently aryl, heteroaryl, substituted aryl, or substitutedheteroaryl; R¹ is H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl; and n is 1 or 2.

In other aspects of this embodiment, a honeybee repellant may be acompound of formula Ic:

wherein: X¹ and X² are each independently N, O or S; L¹ is C₀, C₁-C₆alkyl, C₁-C₆ alkylene, C₂-C₆ alkenyl, C₂-C₆ alkynyl; R¹, R² and R³ areeach independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂₀₁-6 alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl; and n is 1 or 2.

In other aspects of this embodiment, a honeybee repellant may be acompound of formula Id:

wherein: X¹ and X² are each independently N, O or S; L¹ is C₀, C₁-C₆alkyl, C₁-C₆ alkylene, C₂-C₆ alkenyl, C₂-C₆ alkynyl; Ar¹ and Ar² areeach independently aryl, heteroaryl, substituted aryl, or substitutedheteroaryl; and R¹ is H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In other aspects of this embodiment, a honeybee repellant may be acompound of formula Ie:

wherein: X¹ and X² are each independently N, O or S; L¹ is C₀, C₁-C₆alkyl, C₁-C₆ alkylene, C₂-C₆ alkenyl, C₂-C₆ alkynyl; and R¹, R² and R³are each independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In other aspects of this embodiment, a honeybee repellant may be acompound of formula If:

wherein: X¹ and X² are each independently N, O or S; L¹ is C₀, C₁-C₆alkyl, C₁-C₆ alkylene, C₂-C₆ alkenyl, C₂-C₆ alkynyl; Ar¹ and Ar² areeach independently aryl, heteroaryl, substituted aryl, or substitutedheteroaryl; R¹ is H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl; and n is 1 or 2.

In other aspects of this embodiment, a honeybee repellant may be acompound of formula Ig:

wherein: X¹ and X² are each independently N, O or S; L¹ is C₀, C₁-C₆alkyl, C₁-C₆ alkylene, C₂-C₆ alkenyl, C₂-C₆ alkynyl; R¹, R² and R³ areeach independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₀₂₀₁-6 alkyl, CO₂C₂₋₆ alkenyl, orCO₂C₂₋₆ alkynyl; and n is 1 or 2.

In other aspects of this embodiment, a honeybee repellant may be acompound of formula Ih:

wherein: X¹ and X² are each independently N, O or S; L¹ is C₀, C₁-C₆alkyl, C₁-C₆ alkylene, C₂-C₆ alkenyl, C₂-C₆ alkynyl; Ar¹ and Ar² areeach independently aryl, heteroaryl, substituted aryl, or substitutedheteroaryl; and R¹ is H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In other aspects of this embodiment, a honeybee repellant may be acompound of formula Ii:

wherein: X¹ and X² are each independently N, O or S; L¹ is C₀, C₁-C₆alkyl, C₁-C₆ alkylene, C₂-C₆ alkenyl, C₂-C₆ alkynyl; and R¹, R² and R³are each independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In another embodiment, a honeybee repellant may be optionallysubstituted 2-(4-methoxyphenyl)-3-(2-phenylethyl)-1,3-thiazolidin-4-one.In an aspect of this embodiment, a honeybee repellant is2-(4-methoxyphenyl)-3-(2-phenylethyl)-1,3-thiazolidin-4-one.

In an aspect of this embodiment, a honeybee repellant may is not2-(4-methoxyphenyl)-3-(2-phenylethyl)-1,3-thiazolidin-4-one.

In another embodiment, a honeybee repellant may be a compound of formulaII:

wherein: X¹ is N, O, or S; X², and X³ are each independently C, N, O orS; L¹ and L² are each independently C₀, C₁-C₆ alkyl, C₁-C₆ alkylene,C₂-C₆ alkenyl, C₂-C₆ alkynyl; Ar¹ and Ar² are each independently aryl,heteroaryl, substituted aryl, or substituted heteroaryl; each R¹ and R²are each independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen, C(F)₃,C(Cl)₃, C(Br)₃, C(I)₃, trihalomethanesulfonyl,trihalomethanesulfonamido, trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; m is 0-3; nis 1 or 2; and a dashed line represents an optional double bond.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IIa:

wherein: X¹ is N, O, or S; X², and X³ are each independently C, N, O orS; L¹ and L² are each independently C₀, C₁-C₆ alkyl, C₁-C₆ alkylene,C₂-C₆ alkenyl, C₂-C₆ alkynyl; each R¹ and R², R³, and R⁴ are eachindependently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂,C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N,SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O),NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl,halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen, C(F)₃, CO(Cl)₃,C(Br)₃, C(I)₃, trihalomethanesulfonyl, trihalomethanesulfonamido,trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl,CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; m is 0-3; n is 1 or 2; and a dashedline represents an optional double bond.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IIb:

wherein: X¹ is N, O, or S; X², and X³ are each independently C, N, O orS; Ar¹ and Ar² are each independently aryl, heteroaryl, substitutedaryl, or substituted heteroaryl; each R¹ and R² and R⁴ are eachindependently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂,C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N,SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O),NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl,halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen, C(F)₃, C(Cl)₃,C(Br)₃, C(I)₃, trihalomethanesulfonyl, trihalomethanesulfonamido,trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl,CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; m is 0-3; n is 1 or 2; and a dashedline represents an optional double bond.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IIc:

wherein: X¹ and X⁴ are each independently N, O, or S; X², X³, X⁵, X⁶ andX⁷ are each independently C, N, O or S; each R¹ and R², R³, R⁴, and R⁵are each independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen, C(F)₃,C(Cl)₃, C(Br)₃, C(I)₃, trihalomethanesulfonyl,trihalomethanesulfonamido, trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; m is 0-3; nis 1 or 2; and a dashed line represents an optional double bond.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IId:

wherein: X¹ is N, O, or S; X², and X³ are each independently C, N, O orS; Ar¹ and Ar² are each independently aryl, heteroaryl, substitutedaryl, or substituted heteroaryl; R¹, R², and R⁴ are each independentlyH, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂, C(O)NC(O),C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N, SCN, CNS,(N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O), NCS, (N)C(S),NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl, halide,haloalkenyl, haloalkoxyl, haloalkyl, halogen, C(F)₃, C(Cl)₃, C(Br)₃,C(I)₃, trihalomethanesulfonyl, trihalomethanesulfonamido,trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl,CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; and a dashed line represents anoptional double bond.

In aspects of this embodiment, a honeybee repellant may be a compound offormula Ile:

wherein: X¹ and X⁴ are each independently N, O, or S; X², X³, X⁵, X⁶ andX⁷ are each independently C, N, O or S; R¹, R², R³, R⁴, and R⁵ are eachindependently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂,C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N,SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O),NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl,halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen, C(F)₃, C(Cl)₃,C(Br)₃, C(I)₃, trihalomethanesulfonyl, trihalomethanesulfonamido,trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl,CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; and a dashed line represents anoptional double bond.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IIf:

wherein: X¹ and X⁴ are each independently N, O, or S; X³, X⁵, X⁶ and X⁷are each independently C, N, O or S; Ar¹ is aryl, heteroaryl,substituted aryl, or substituted heteroaryl; R¹, R², R⁴, and R⁵ are eachindependently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂,C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N,SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O),NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl,halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen, C(F)₃, C(Cl)₃,C(Br)₃, C(I)₃, trihalomethanesulfonyl, trihalomethanesulfonamido,trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl,CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; and a dashed line represents anoptional double bond.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IIg:

wherein: X¹ and X⁴ are each independently N, O, or S; X³, X⁵, X⁶ and X⁷are each independently C, N, O or S; R¹, R², R³, R⁴, and R⁵ are eachindependently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂,C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N,SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O),NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl,halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen, C(F)₃, C(Cl)₃,C(Br)₃, C(I)₃, trihalomethanesulfonyl, trihalomethanesulfonamido,trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl,CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; and a dashed line represents anoptional double bond.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IIh:

wherein: X¹ and X⁴ are each independently N, O, or S; X³ is C, N, O orS; Ar¹ is aryl, heteroaryl, substituted aryl, or substituted heteroaryl;R¹, R², R⁴, and R⁵ are each independently H, OH, OOH, O, OO, C(O),C(O)H, C(O)OH, OC(O)O, C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N,OCN, NHC(O)O, CS, C(S)H, OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN,NN, N(OH), NC, NCO, (N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O),S(O)₂, S(O)₃, S(O)₂N, aminoalkyl, halide, haloalkenyl, haloalkoxyl,haloalkyl, halogen, C(F)₃, C(Cl)₃, C(Br)₃, C(I)₃,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl; and a dashed line represents an optional double bond.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IIi:

wherein: X¹ and X⁴ are each independently N, O, or S; X³ is C, N, O orS; R¹, R², R³, R⁴, and R⁵ are each independently H, OH, OOH, O, OO,C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH,C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N, SCN, CNS, (N)C(S), NH, NH₂,NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH,S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl, halide, haloalkenyl,haloalkoxyl, haloalkyl, halogen, C(F)₃, C(Cl)₃, C(Br)₃, C(I)₃,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl; and a dashed line represents an optional double bond.

In another embodiment, a honeybee repellant may be optionallysubstituted5-phenyl-1-(8-quinolinyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-ol.In an aspect of this embodiment, a honeybee repellant is5-phenyl-1-(8-quinolinyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-ol.

In an aspect of this embodiment, a honeybee repellant is not5-phenyl-1-(8-quinolinyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-ol.

In another embodiment, a honeybee repellant may be a compound of formulaIII:

wherein: X¹, and X⁵ are each independently N, O, or S; X², X³, X⁴, andX⁶ are each independently C, N, O or S; L¹ is C₀, C₁-C₆ alkyl, C₁-C₆alkylene, C₂-C₆ alkenyl, C₂-C₆ alkynyl; and Ar¹ and Ar² are eachindependently aryl, heteroaryl, substituted aryl, or substitutedheteroaryl; R¹ and R² are each independently H, OH, OOH, O, OO, C(O),C(O)H, C(O)OH, OC(O)O, C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N,OCN, NHC(O)O, CS, C(S)H, OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN,NN, N(OH), NC, NCO, (N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O),S(O)₂, S(O)₃, S(O)₂N, aminoalkyl, halide, haloalkenyl, haloalkoxyl,haloalkyl, halogen, C(F)₃, C(Cl)₃, C(Br)₃, C(I)₃,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, CO₂C₂₋₆alkynyl, NC₁₋₆ alkyl, NC₂₋₆ alkenyl, NC₂₋₆ alkynyl, N(C₁₋₆ alkyl)₂,N(C₂₋₆ alkenyl)₂, or N(C₂₋₆ alkynyl)₂.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IIIa:

wherein: X¹, and X⁵ are each independently N, O, or S; X², X³, X⁴, andX⁶ are each independently C, N, O or S; L¹ is C₀, C₁-C₆ alkyl, C₁-C₆alkylene, C₂-C₆ alkenyl, C₂-C₆ alkynyl; and R¹, R², R³, and R⁴ are eachindependently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂,C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N,SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O),NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl,halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen, C(F)₃, C(Cl)₃,C(Br)₃, C(I)₃, trihalomethanesulfonyl, trihalomethanesulfonamido,trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl,CO₂C₂₋₆ alkenyl, CO₂C₂₋₆ alkynyl, NC₁₋₆ alkyl, NC₂₋₆ alkenyl, NC₂₋₆alkynyl, N(C₁₋₆ alkyl)₂, N(C₂₋₆ alkenyl)₂, or N(C₂₋₆ alkynyl)₂.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IIIb:

wherein: X¹, and X⁵ are each independently N, O, or S; X², X³, X⁴, andX⁶ are each independently C, N, O or S; Ar¹ and Ar² are eachindependently aryl, heteroaryl, substituted aryl, or substitutedheteroaryl; and R¹ and R² are each independently H, OH, OOH, O, OO,C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH,C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N, SCN, CNS, (N)C(S), NH, NH₂,NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH,S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl, halide, haloalkenyl,haloalkoxyl, haloalkyl, halogen, C(F)₃, C(Cl)₃, C(Br)₃, C(I)₃,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, CO₂C₂₋₆alkynyl, NC₁₋₆ alkyl, NC₂₋₆ alkenyl, NC₂₋₆ alkynyl, N(C₁₋₆ alkyl)₂,N(C₂₋₆ alkenyl)₂, or N(C₂₋₆ alkynyl)₂.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IIIc:

wherein: X¹, and X⁵ are each independently N, O, or S; X², X³, X⁴, andX⁶ are each independently C, N, O or S; and R¹, R², R³, and R⁴ are eachindependently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂,C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N,SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O),NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl,halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen, C(F)₃, C(Cl)₃,C(Br)₃, C(I)₃, trihalomethanesulfonyl, trihalomethanesulfonamido,trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl,CO₂C₂₋₆ alkenyl, CO₂C₂₋₆ alkynyl, NC₁₋₆ alkyl, NC₂₋₆ alkenyl, NC₂₋₆alkynyl, N(C₁₋₆ alkyl)₂, N(C₂₋₆ alkenyl)₂, or N(C₂₋₆ alkynyl)₂.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IIId:

wherein: X¹, and X⁵ are each independently N, O, or S; Ar¹ and Ar² areeach independently aryl, heteroaryl, substituted aryl, or substitutedheteroaryl; and each R¹ and R² are each independently H, OH, OOH, O, OO,C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH,C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N, SCN, CNS, (N)C(S), NH, NH₂,NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH,S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl, halide, haloalkenyl,haloalkoxyl, haloalkyl, halogen, C(F)₃, C(Cl)₃, C(Br)₃, C(I)₃,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, CO₂C₂₋₆alkynyl, NC₁₋₆ alkyl, NC₂₋₆ alkenyl, NC₂₋₆ alkynyl, N(C₁₋₆ alkyl)₂,N(C₂₋₆ alkenyl)₂, or N(C₂₋₆ alkynyl)₂.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IIIe:

wherein: X¹, and X⁵ are each independently N, O, or S; each R¹ and R²,R³, and R⁴ are each independently H, OH, OOH, O, OO, C(O), C(O)H,C(O)OH, OC(O)O, C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN,NHC(O)O, CS, C(S)H, OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN,N(OH), NC, NCO, (N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂,S(O)₃, S(O)₂N, aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl,halogen, C(F)₃, C(Cl)₃, C(Br)₃, C(I)₃, trihalomethanesulfonyl,trihalomethanesulfonamido, trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, CO₂C₂₋₆ alkynyl, NC₁₋₆ alkyl,NC₂₋₆ alkenyl, NC₂₋₆ alkynyl, N(C₁₋₆ alkyl)₂, N(C₂₋₆ alkenyl)₂, orN(C₂₋₆ alkynyl)₂.

In another embodiment, a honeybee repellant may be optionallysubstituted(3-amino-6-phenylthieno[2,3-b]pyridin-2-yl)(phenyl)methanone. In anaspect of this embodiment, a honeybee repellant is(3-amino-6-phenylthieno[2,3-b]pyridin-2-yl)(phenyl)methanone.

In an aspect of this embodiment, a honeybee repellant is not(3-amino-6-phenylthieno[2,3-b]pyridin-2-yl)(phenyl)methanone.

In another embodiment, a honeybee repellant may be a compound of formulaIV:

wherein: X¹ and X² are each independently N, O or S; R¹, R², and R³ areeach independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl; and n is 1 or 2.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IVa:

wherein: X¹ and X² are each independently N, O or S; and R¹, R², and R³are each independently H, OH, OOH, O, O, OO, C(O), C(O)H, C(O)OH,OC(O)O, C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS,C(S)H, OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC,NCO, (N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃,S(O)₂N, aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IVb:

wherein: X¹ and X² are each independently N or O; and R¹, R², and R³ areeach independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NC(O), halide, haloalkenyl, haloalkoxyl, haloalkyl, oxoalkyl,oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl, OC₂₋₆alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IVc:

wherein: X¹ and X² are each independently N, O or S; and R¹, R², and R³are each independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IVd:

wherein: X¹ and X² are each independently N or O; and R¹, R², and R³ areeach independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NC(O), halide, haloalkenyl, haloalkoxyl, haloalkyl, oxoalkyl,oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl, OC₂₋₆alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IVe:

wherein: X¹ and X² are each independently N, O or S; and R¹, R², and R³are each independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IVf:

wherein: X¹ and X² are each independently N or O; and R¹, R², and R³ areeach independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NC(O), halide, haloalkenyl, haloalkoxyl, haloalkyl, oxoalkyl,oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl, OC₂₋₆alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IVg:

wherein: X¹ and X² are each independently N, O or S; and R¹, R², and R³are each independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IVh:

wherein: X¹ and X² are each independently N or O; and R¹, R², and R³ areeach independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NC(O), halide, haloalkenyl, haloalkoxyl, haloalkyl, oxoalkyl,oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl, OC₂₋₆alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IVi:

wherein: X¹ and X² are each independently N, O or S; and R¹, R², and R³are each independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IVj:

wherein: X¹ and X² are each independently N or O; and R¹, R², and R³ areeach independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NC(O), halide, haloalkenyl, haloalkoxyl, haloalkyl, oxoalkyl,oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl, OC₂₋₆alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl.

In aspects of this embodiment, a honeybee repellant may be a compound offormula IVk:

where: X¹ and X² are each independently N or O; R¹ and R are eachindependently H, OH, OOH, O, C₁₋₆ alkyl, halide, or halogen; R³ is C(O),C(O)H, C(O)OH, OC(O)O, C(O)NC(O), halide, haloalkenyl, haloalkoxyl,haloalkyl, oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,OC₁₋₆ alkyl, OCH₂CH₃, OC₂₋₆ alkenyl, OCH₂CH₂, OC₂₋₆ alkynyl, CO₂C₁₋₆alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; and n is 1 or 2.

n aspects of this embodiment, a honeybee repellant of formula IVdisclosed herein may be an optionally substituted2-(4-ethoxy-6-methyl-2-pyrimidinyl)phenol or an optionally substituted2-[4-(allyloxy)-6-methyl-2-pyrimidinyl]phenol. In an aspect of thisembodiment, a honeybee repellant is2-(4-ethoxy-6-methyl-2-pyrimidinyl)phenol or2-[4-(allyloxy)-6-methyl-2-pyrimidinyl]phenol.

In an aspect of this embodiment, a honeybee repellant is not2-(4-ethoxy-6-methyl-2-pyrimidinyl)phenol or2-[4-(allyloxy)-6-methyl-2-pyrimidinyl]phenol.

In some embodiments, a honeybee repellent may be an optionallysubstituted ethyl2-[(2,2-dimethylpropanoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate,an optionally substitutedN-(3,4-dihydro-1(2H)-quinolinylcarbonothioyl)benzamide, or an optionallysubstituted N-[3-(4-methoxyphenyl)-1-methylpropyl]-4-morpholinamine. Inaspects of this embodiment, a honeybee repellant is ethyl2-[(2,2-dimethylpropanoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate,N-(3,4-dihydro-1 (2H)-quinolinylcarbonothioyl)benzamide, orN-[3-(4-methoxyphenyl)-1-methylpropyl]-4-morpholinamine.

In some embodiments, a honeybee repellent is not ethyl2-[(2,2-dimethylpropanoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate.In some embodiments, a honeybee repellent is notN-(3,4-dihydro-1(2H)-quinolinylcarbonothioyl)benzamide. In someembodiments, a honeybee repellent is notN-[3-(4-methoxyphenyl)-1-methylpropyl]-4-morpholinamine.

Aspects of the present specification provide, in part, a compositioncomprising a honeybee repellent disclosed herein. A compositiondisclosed herein comprises a repellent compound disclosed herein and isuseful in repelling honeybees from an individual and/or a locationtreated with the composition. As such, a composition disclosed herein isuseful for any application that reduces bee-human interaction or abee-location interaction. A composition may be administered to anindividual or location alone, or in combination with other supplementaryactive ingredients, agents, or drugs.

A composition disclosed herein may comprise one or more honeybeerepellents disclosed herein. In one embodiment, a composition disclosedherein may comprise only a single a honeybee repellent disclosed herein.In another embodiment, a composition disclosed herein may comprise aplurality of honeybee repellents disclosed herein. In aspects of thisembodiment, a composition disclosed herein comprises at least twohoneybee repellents, at least three honeybee repellents, at least fourhoneybee repellents, or at least five honeybee repellents. In otheraspects of this embodiment, a composition disclosed herein comprises atmost two honeybee repellents, at most three honeybee repellents, or atmost four honeybee repellents. In yet other aspects of this embodiment,a composition disclosed herein comprises one to three honeybeerepellents, two to four honeybee repellents, two to five honeybeerepellents, three to five honeybee repellents, or two to three honeybeerepellents.

In an embodiment, a composition disclosed herein includes a repellent offormula I, formula II, formula III, formula IV, formula V, formula VI,formula VII, formula VIII, formula IX, formula X, formula XI, formulaXII, formula XIII, or any combination thereof.

In an embodiment, a composition disclosed herein has a honeybeerepellency activity. In aspects of this embodiment, presence of acomposition repels honeybees by, e.g., at least 10%, at least 15%, atleast 20%, at least 25%, at least 30%, at least 35%, at least 40%, atleast 45%, at least 50%, at least 55%, at least 60%, at least 65%, atleast 70%, at least 75%, at least 80%, at least 85%, at least 90%, or atleast 95%, as compared to not having the composition present. In otheraspects of this embodiment, presence of a composition repels honeybeesby, e.g., about 10% to about 100%, about 20% to about 100%, about 30% toabout 100%, about 40% to about 100%, about 50% to about 100%, about 60%to about 100%, about 70% to about 100%, about 80% to about 100%, about10% to about 90%, about 20% to about 90%, about 30% to about 90%, about40% to about 90%, about 50% to about 90%, about 60% to about 90%, about70% to about 90%, about 10% to about 80%, about 20% to about 80%, about30% to about 80%, about 40% to about 80%, about 50% to about 80%, orabout 60% to about 80%, about 10% to about 70%, about 20% to about 70%,about 30% to about 70%, about 40% to about 70%, or about 50% to about70%, as compared to not having the composition present.

In an embodiment, a composition disclosed herein reduces a honeybeeinteraction with a mammal or location. In aspects of this embodiment, acomposition reduces honeybee interaction with a mammal or location by,e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least30%, at least 35%, at least 40%, at least 45%, at least 50%, at least55%, at least 60%, at least 65%, at least 70%, at least 75%, at least80%, at least 85%, at least 90%, or at least 95%. In other aspects ofthis embodiment, a composition reduces honeybee interaction with amammal or location by, e.g., about 10% to about 100%, about 20% to about100%, about 30% to about 100%, about 40% to about 100%, about 50% toabout 100%, about 60% to about 100%, about 70% to about 100%, about 80%to about 100%, about 10% to about 90%, about 20% to about 90%, about 30%to about 90%, about 40% to about 90%, about 50% to about 90%, about 60%to about 90%, about 70% to about 90%, about 10% to about 80%, about 20%to about 80%, about 30% to about 80%, about 40% to about 80%, about 50%to about 80%, or about 60% to about 80%, about 10% to about 70%, about20% to about 70%, about 30% to about 70%, about 40% to about 70%, orabout 50% to about 70%.

In an embodiment, a composition disclosed herein reduces an ability of ahoneybee to obtain a meal from a plant. In aspects of this embodiment, acomposition reduces an ability of a honeybee to obtain a meal from aplant by, e.g., at least 10%, at least 15%, at least 20%, at least 25%,at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, or at least 95%. In other aspectsof this embodiment, a composition reduces an ability of a honeybee toobtain a meal from a plant by, e.g., about 10% to about 100%, about 20%to about 100%, about 30% to about 100%, about 40% to about 100%, about50% to about 100%, about 60% to about 100%, about 70% to about 100%,about 80% to about 100%, about 10% to about 90%, about 20% to about 90%,about 30% to about 90%, about 40% to about 90%, about 50% to about 90%,about 60% to about 90%, about 70% to about 90%, about 10% to about 80%,about 20% to about 80%, about 30% to about 80%, about 40% to about 80%,about 50% to about 80%, or about 60% to about 80%, about 10% to about70%, about 20% to about 70%, about 30% to about 70%, about 40% to about70%, or about 50% to about 70%.

A composition disclosed herein can take any of a variety of dosage formsincluding, without limitation, a liquid composition, such as, e.g., asolution, suspension, emulsion; a semi-solid composition, such as, e.g.,a ointment, cream, balm, foam, gel, or salve or a solid composition,such as, e.g., lyophilizate, powder, granule, pellet, capsule; or anyother dosage form suitable for applying a repellent compound disclosedherein to a mammal, plant, and/or location to be treated. In oneembodiment, in liquid, semi-solid, and solid forms, an amount of arepellent compound disclosed herein typically is between about 0.0001%(w/v) to about 50% (w/v), about 0.001% (w/v) to about 10.0% (w/v), orabout 0.01% (w/v) to about 1.0% (w/v). In another aspect embodiment, inliquid, semi-solid, and solid forms, an amount of a repellent compounddisclosed herein typically is between about 0.001 μg/cm² to about 500μg/cm², about 0.01 μg/cm² to about 100 μg/cm², or about 0.1 μg/cm² toabout 10 μg/cm². In another aspect embodiment, in liquid, semi-solid,and solid forms, an amount of a repellent compound disclosed hereintypically is between about 0.01 nmole/cm² to about 1000 nmole/cm², about0.1 nmole/cm² to about 100 nmole/cm², or about 1 nmole/cm² to about 50nmole/cm². In another embodiment, in liquid, semi-solid, and solidforms, an amount of a repellent compound disclosed herein is typicallyis between about 0.001 mg/L to about 500 mg/L, about 0.01 mg/L to about100 mg/L, or about 0.1 mg/L to about 50 mg/L.

The amount of a honeybee repellent disclosed herein used in thecompositions disclosed herein is an effective amount. As used herein,the term “effective amount” refers to an amount of a honeybee repellentor composition disclosed herein sufficient to repel or direct movementof honeybees to the source of repellent compound release.

In aspects of this embodiment, a composition comprises a honeybeerepellent in an effective amount of, e.g., at least 0.0001%, at least0.00025%, at least 0.0005%, at least 0.00075%, at least 0.001%, at least0.0025%, at least 0.005%, at least 0.0075%, at least 0.01%, at least0.025%, at least 0.05%, at least 0.075%, at least 0.1%, at least 0.25%,at least 0.5%, at least 0.75%, at least 1%, at least 2.5%, at least 5%,at least 7.5%, at least 10%, at least 25%, or at least 50%, by weight ofa composition.

In other aspects of this embodiment, a composition comprises a honeybeerepellent in an effective amount of between, e.g., about 0.0001% toabout 0.001%, about 0.0001% to about 0.01%, about 0.0001% to about 0.1%,about 0.00025% to about 0.0025%, about 0.00025% to about 0.025%, about0.00025% to about 0.25%, about 0.0005% to about 0.005%, about 0.0005% toabout 0.05%, about 0.0005% to about 0.75%, about 0.00075% to about0.0075%, about 0.00075% to about 0.075%, about 0.00075% to about 0.75%,about 0.001% to about 0.01%, about 0.001% to about 0.1%, about 0.001% toabout 1%, about 0.0025% to about 0.025%, about 0.0025% to about 0.25%,about 0.0025% to about 2.5%, about 0.005% to about 0.05%, about 0.005%to about 0.5%, about 0.005% to about 5%, about 0.0075% to about 0.075%,about 0.0075% to about 0.75%, about 0.0075% to about 7.5%, about 0.01%to about 0.1%, about 0.01% to about 1%, about 0.01% to about 10%, about0.025% to about 0.25%, about 0.025% to about 2.5%, about 0.025% to about25%, about 0.05% to about 0.5%, about 0.05% to about 5%, about 0.05% toabout 50%, about 0.075% to about 0.75%, about 0.075% to about 7.5%, orabout 0.075% to about 75%, by weight of a composition. In yet otheraspects of this embodiment, a composition comprises a honeybee repellentin an effective amount of between, e.g., about 0.005% to about 0.015%,about 0.0025% to about 0.025%, or about 0.006% to about 0.016%, byweight of a composition.

A composition disclosed herein may optionally comprise one or moreadditional compounds providing an additional beneficial or otherwiseuseful effect. Such compounds include, without limitation, an adhesive,a solvent, a wetting agent, an emulsifying agent, a carrier, a diluent,a dispersing agent an insecticide, a pesticide, a fungicide, afertilizer of a micronutrient or macronutrient nature, a herbicide, afeeding inhibitor, an insect molting inhibitor, an insect matinginhibitor, an insect maturation inhibitor, a nematocide, a nutritionalor horticultural supplement, a larvicide, a seed, or any combinationthereof. Such compounds are known to a person of ordinary skill in theart.

In one aspect of this embodiment, a composition disclosed herein mayoptionally comprise an insecticide. In another aspect of thisembodiment, a composition disclosed herein may optionally comprise aplurality of insecticides. Insecticides include oils, emulsifers,detergents, soaps, microorganisms like fungi, bacteria, bacteriophages,and viruses, abrasives, toxins, and poisons. Non-limiting examples of aninsecticide include a organochlorine, such as, e.g., Aldrin, Chlordane,Chlordecone, DDT, Dieldrin, Endosulfan, Endrin, Heptachlor,Hexachlorobenzene, Lindane (gamma-hexachlorocyclohexane), Methoxychlor,Mirex, Pentachlorophenol, and TDE; an organophosphate, such as, e.g.,Acephate, Azinphos-methyl, Bensulide, Chlorethoxyfos, Chlorpyrifos,Chlorpyriphos-methyl, Diazinon, Dichlorvos (DDVP), Dicrotophos,Dimethoate, Disulfoton, Ethoprop, Fenamiphos, Fenitrothion, Fenthion,Fosthiazate, Malathion, Methamidophos, Methidathion, Mevinphos,Monocrotophos, Naled, Omethoate, Oxydemeton-methyl, Parathion,Parathion-methyl, Phorate, Phosalone, Phosmet, Phostebupirim, Phoxim,Pirimiphos-methyl, Profenofos, Terbufos, Tetrachlorvinphos, Tribufos,and Trichlorfon; a carbamate, such as, e.g., Aldicarb, Bendiocarb,Carbofuran, Carbaryl, Dioxacarb, Fenobucarb, Fenoxycarb, Isoprocarb,Methomyl, and 2-(1-Methylpropyl)phenyl methylcarbamate; a pyrethroid,such as, e.g., Allethrin, Bifenthrin, Cyhalothrin, λ-Cyhalothrin,Cypermethrin, Cyfluthrin, Deltamethrin, Etofenprox, Fenvalerate,Permethrin, Phenothrin, Prallethrin, Resmethrin, Tetramethrin,Tralomethrin, and Transfluthrin; a neonicotinoid, such as, e.g.,Acetamiprid, Clothianidin, Imidacloprid, Nitenpyram, Nithiazine,Thiacloprid, and Thiamethoxam; and a spinosad, such as, e.g., spinosyn Aand spinosyn B.

The present specification provides, in part, a composition comprising arepellent compound or a composition providing an additional beneficialor otherwise useful effect that is coated, encapsulated or otherwisecovered with a honeybee repellent or a composition comprising a honeybeerepellent disclosed herein. Additionally, the present specificationprovides, in part, a composition comprising a honeybee repellent or acomposition comprising a honeybee repellent disclosed herein that iscoated, encapsulated or otherwise covered with another compound orcomposition providing an additional beneficial or otherwise usefuleffect. The compositions disclosed herein are formulated to repelhoneybees from a location where the compositions were intentionally orunintentionally deposited and at the same time provide an additionalbeneficial or otherwise useful effect.

When used to coat another substance, a honeybee repellent or compositioncomprising a honeybee repellent disclosed herein, or a compound orcomposition providing an additional beneficial or otherwise usefuleffect disclosed herein are formulated in a manner that will allow therepellent, compound, or compositions thereof to adhere to the othersubstance. Typically, a repellent, a compound, or a composition thereofare mixed with a coating material and processed into a formulation suchas, e.g., a solid, a gel, a liquid, a suspension in aqueous ornon-aqueous medium, an emulsion, or a foam. Such coating materials andadhering methods are known to a person of ordinary skill in the art.

For example, a honeybee repellent can be mixed with a wax and theresulting mixture is then adhered to a compound providing an additionalbeneficial or otherwise useful effect in a manner that ensures thecompound is coated, encapsulated or otherwise covered by the mixture. Inone aspect, a honeybee repellent can be mixed with a wax and theresulting mixture is then adhered to a seed in a manner that ensures theseed is coated, encapsulated or otherwise covered by the mixture. Inanother aspect, a honeybee repellent can be mixed with a wax and theresulting mixture is then adhered to an insecticide in a manner thatensures the insecticide is coated, encapsulated or otherwise covered bythe mixture. In yet another aspect, a honeybee repellent and aninsecticide can be mixed with a wax and the resulting mixture is thenadhered to a seed in a manner that ensures the seed is coated,encapsulated or otherwise covered by the mixture.

In another embodiment, an appropriate amount of a honeybee repellentdisclosed herein can be dissolved into an appropriate compatible solventand the resulting mixture is then adhered to a compound providing anadditional beneficial or otherwise useful effect in a manner thatensures the compound is coated, encapsulated or otherwise covered by themixture. The solvent employed is typically a volatile solvent (i.e.,having a boiling point of about 100° C. or less) that will evaporateover a period of time. In one aspect, a honeybee repellent can be mixedwith a solvent and the resulting mixture is then adhered to a seed in amanner that ensures the seed is coated, encapsulated or otherwisecovered by the mixture. In another aspect, a honeybee repellent can bemixed with a solvent and the resulting mixture is then adhered to aninsecticide in a manner that ensures the insecticide is coated,encapsulated or otherwise covered by the mixture. In yet another aspect,a honeybee repellent and an insecticide can be mixed with a solvent andthe resulting mixture is then adhered to a seed in a manner that ensuresthe seed is coated, encapsulated or otherwise covered by the mixture.

In one aspect of this embodiment, one or more insecticides, pesticides,fungicides, fertilizers of a micronutrient or macronutrient nature,herbicides, feeding inhibitors, insect molting, insect mating, insectmaturation inhibitors, nematocides, nutritional or horticulturalsupplements, larvicides, seeds, and any combination thereof is coated,encapsulated or otherwise covered with one or more honeybee repellentsor compositions comprising a honeybee repellent disclosed herein.

In another aspect of this embodiment, a honeybee repellent orcompositions disclosed herein is coated, encapsulated or otherwisecovered with one or more insecticides, pesticides, fungicides,fertilizers of a micronutrient or macronutrient nature, herbicides,feeding inhibitors, insect molting, insect mating, insect maturationinhibitors, nematocides, nutritional or horticultural supplements,larvicides, seeds, and any combination thereof.

In yet another aspect of this embodiment, seeds are coated, encapsulatedor otherwise covered with one or more honeybee repellents orcompositions comprising a honeybee repellent disclosed herein. Thesecompositions are formulated to repel honeybees from the seed, and thusfrom a field, yard, pot, area, or body of water onto which the seedswere intentionally or unintentionally present.

In still another aspect of this embodiment, seeds are coated,encapsulated or otherwise covered with one or more honeybee repellentsor compositions comprising a honeybee repellent disclosed herein and oneor more insecticides, pesticides, fungicides, fertilizers of amicronutrient or macronutrient nature, herbicides, feeding inhibitors,insect molting, insect mating, insect maturation inhibitors,nematocides, nutritional or horticultural supplements, or larvicides.These compositions are formulated to repel honeybees from the seed, andthus from a field, yard, pot, area, or body of water onto which theseeds were be intentionally or unintentionally present as well asprovide an additional beneficial or otherwise useful effect.

In another embodiment, a honeybee repellent or composition disclosedherein is incorporated into a device. As used herein, the term “device”refers to any device designed to house and/or shelter, a honeybeerepellent or compositions disclosed herein. A device disclosed hereinmay be a container, holder or other solid support onto or into which ahoneybee repellent or composition disclosed herein. A device disclosedherein may be made form any biological or synthetic material, including,without limitation, paper, filter paper, wood, cork, cotton, plastic,polymer, metal, or glass.

Aspects of the present specification disclose a use of a honeybeerepellent disclosed herein to repel a honeybee from a location treatedwith the honeybee repellent. In one embodiment, the disclosed use is ause of a honeybee repellent disclosed herein to repel a honeybee fromforaging and/or collecting nectar from a flower of a plant treated withthe honeybee repellent. In another embodiment, the disclosed use is ause of a honeybee repellent disclosed herein to repel a honeybee from astructure treated with the honeybee repellent.

Aspects of the present specification disclose a method of treating alocation by applying a honeybee repellent disclosed herein, wherein suchapplication repels a honeybee from the treated location. In oneembodiment, the disclosed method is a method of treating a plant byapplying a honeybee repellent disclosed herein, wherein such applicationrepels a honeybee from foraging and/or collecting nectar from a flowerof the treated plant. In another embodiment, the disclosed method is amethod of treating a structure by applying a honeybee repellentdisclosed herein, wherein such application repels a honeybee from thetreated structure.

Aspects of the present specification disclose a method of reducing orpreventing a honeybee foraging to a location by applying a honeybeerepellent or composition disclosed herein, wherein such applicationrepels honeybees from the location, thereby reducing or preventing thehoneybee foraging. In one embodiment, the disclosed method is a methodof treating a plant by applying a honeybee repellent or compositiondisclosed herein, wherein such application repels a honeybee fromforaging for a meal in the vicinity of the treated plant, flower, orseed. In another embodiment, the disclosed method is a method oftreating a structure by applying a honeybee repellent or compositiondisclosed herein, wherein such application repels a honeybee fromforaging for a meal in the vicinity of the treated structure.

As used herein, the term “location” refers to any site to which movementof a honeybee is to be retarded. A location includes, by way of example,a plant or group of plants or part of a plant, a particular area ofland, or a man-made structure, such as, e.g., a commercial building, ahouse, a shed, or other physical structure. As used herein, the term“plant” refers to any living organism belonging to the Kingdom Plantae.Non-limiting examples include trees, flowering plant, herbs, bushes,grasses, vines, ferns, mosses, and green algae. As used herein, the term“flower” is synonymous with “bloom” or “blossom” and refers thereproductive structure found in angiosperms. As used herein, the term“crop plant” refers to a plant that produces a crop. Non-limitingexamples include are plants that produce fruits, seeds, nuts, grains,oil, wood, and fibers. As used herein, the term “crop” refers to a plantproduct which is of economical value. Non-limiting examples include arefruits, seeds, nuts, grains, oil, wood, and fibers.

A honeybee repellent or composition disclosed herein is applied to alocation by any method that can dispense to a location an amount ofhoneybee repellent effective in repelling a honeybee. A method ofapplication is not critical and many well known methods can be used. Inone embodiment, an appropriate amount of a honeybee repellent orcomposition disclosed herein can be dissolved into an appropriatecompatible solvent and dispensed as a solution onto the intendedlocation. The solvent employed is typically a volatile solvent (i.e.,having a boiling point of about 100° C. or less) that will evaporateover a period of time. In another embodiment, an appropriate amount of ahoneybee repellent or composition disclosed herein can be combined withan appropriate propellant and used as a spray for application onto theintended location.

In another embodiment, a honeybee repellent or composition disclosedherein can be impregnated into a compatible matrix. As used herein, theterm “compatible matrix” refers to any material in which one or morerepellent compounds disclosed herein are either soluble or miscible andwhere the material does not significantly alter or degrade theattractant activity of the one or more repellent compound. In aspects ofthis embodiment, a compatible matrix does not significantly alter ordegrade an attractant activity of one or more honeybee repellents over aperiod of, e.g., at least 7 days, at least 14 days, at least 21 days, atleast 28 days, at least 35 days, at least 42 days, at least 49 days, atleast 56 days, or at least 63 days. Impregnation of a repellent compoundinto the compatible matrix can be achieved by any well known methodsknown in the art. For example, a honeybee repellent can be dissolvedinto a compatible volatile solvent and the resulting solution added tothe matrix whereupon evaporation of the solvent results in impregnationof the repellent compound into the compatible matrix. In this regard,the matrix can be cotton twine, polymers such as, e.g., polyvinyls,polyisoprenes, polyethylene, polypropylene or copolymers thereof, orpolybutenes. In another example, a compatible matrix is thinned byheating and then a repellent compound is added directly thereto. Themixture can then be combined with twine or other compatible matrices. Acompatible matrix disclosed herein may be employed by itself orincorporated into a device used to house the matrix.

In another embodiment, a honeybee repellent or composition disclosedherein can be incorporated into a controlled-release device whichdispenses a honeybee repellent and/or other beneficial compound overtime in a regulated or predictable manner. A controlled-release devicedisclosed herein may be employed by itself or incorporated into anotherdevice used to house the controlled-release device.

One type of controlled-release device is a “reservoir” device where ahoneybee repellent or composition forms a core surrounded by an inertdiffusion barrier. An inert diffusion barrier includes membranes whichare non-porous, homogeneous polymeric films, through which transportoccurs by a process of dissolution of the permeating species in thepolymer at one interface and diffusion down a gradient in thermodynamicactivity. These membranes are usually referred to as solution-diffusionmembranes. Another class inert diffusion barrier includes the porousand/or fibrous barriers such as, for example, hollow fibers, porousand/or fibrous materials, in which a repellent compound diffuses mainlyby capillary forces. Other less common reservoir devices are designed toenable diffusion to take place by mechanical pumping or under externalforces, such as, e.g., gravity, electrical field, vacuum, or centrifugalforces. A reservoir device can exist in a variety of shapes, and can bedegradable or non-degradable.

In an aspect of this embodiment, a reservoir device is a microcapsulecomprising a core of a honeybee repellent or composition disclosedherein surrounded by a coating or shell of, e.g., a polyvinyl chloride(PVC)-polyvinyl acetate (PVA) plastic. Size typically varies from about1 μm to about 1000 μm and can have irregular or geometric shapes. Corepayload usually varies from 0.1 to 98 weight percent. Encapsulationprocesses are often loosely classified as either chemical or mechanical.Examples of chemical processes include but are not limited to complexcoacervation, polymer-polymer incompatibility, interfacialpolymerization in liquid media, in situ polymerization, in-liquiddrying, thermal and ionic gelation in liquid media, desolvation inliquid media, starch-based chemistry processes, trapping incyclodextrins, and formation of liposomes. Examples of mechanicalprocesses include but are not limited to spray drying, spray chilling,fluidized bed, electrostatic deposition, centrifugal extrusion, spinningdisk or rotational suspension separation, annular-jet encapsulation,polymerization at liquid-gas or solid-gas interface, solventevaporation, pressure extrusion or spraying into solvent extractionbath.

Another type of controlled-release device is a “monolithic” device wherea honeybee repellent or composition is dissolved or dispersed throughouta substantially inert matrix from which the repellent compound and/orother beneficial compound is gradually released. Non-limiting examplesof matrices included in a monolithic device include various gels, waxes,gelatins, natural resins, rubbers, elastomers, synthetic and naturalpolymers. A monolithic device can exist in a variety of shapes, and canbe degradable or non-degradable. Size can vary depending on theapplication. For example, a monolithic device can be produced as amicrocapsule having a size of about 1 μm to about 1000 μm with irregularor geometric shapes. As another example, a monolithic device can have asize of about 1 mm to about 10 cm with irregular or geometric shape.

A controlled-release device disclosed herein can be a liquid compositionor a solid composition. A liquid sustained-release formulation includesa honeybee repellent or composition disclosed herein, a solvent, andtypically further comprise surface active agents to render thecomposition readily dispersible in water, such agents include a wettingagent, an emulsifying agent, or a dispersing agent. In one embodiment, aliquid form of a sustained-release formulation is an emulsionformulation, such as, e.g., a water in oil (w/o) emulsion or oil inwater (o/w) emulsion. Non-limiting examples of oils include vegetableoils and mineral oils. Droplet size can vary from the nanometer scale(colloidal dispersion) to several hundred microns. A variety ofsurfactants and thickeners are usually incorporated in the formulationto modify the size of the droplets, stabilize the emulsion, and modifythe release.

A solid form of controlled-release device comprises a solid substratelike porous particulates such as silica, perlite, talc, clay,pyrophyllite, diatomaceous earth, gelatin and gels, polymers (e.g.,polyurea, polyurethane, polyamide, polyester, etc.), polymericparticles, or cellulose. These include, for example, hollow fibers,hollow tubes or tubing which release a repellent compound disclosedherein through the walls, capillary tubing which releases the compoundout of an opening in the tubing, polymeric blocks of different shapes,e.g., strips, blocks, tablets, discs, which release the compound out ofthe polymer matrix, membrane systems which hold the repellent compoundwithin an impermeable container and release it through a measuredpermeable membrane, and combinations of the foregoing. Examples of otherdispensing means are polymer laminates, polyvinyl chloride pellets, andmicrocapillaries.

Controlled release can also be achieved by a number of other methodssuch as, e.g., complexation of a honeybee repellent or composition,slowly dissolving coatings, erosion, microbial action, or use ofderivatives or new compounds of reduced solubility or volatility.

In aspects of this embodiment, a controlled-release device releases ahoneybee repellent or composition disclosed herein with substantiallyzero order release kinetics over a period of, e.g., about 7 days, about15 days, about 30 days, about 45 days, about 60 days, about 75 days, orabout 90 days. In other aspects of this embodiment, a controlled-releasedevice releases a honeybee repellent or composition disclosed hereinwith substantially zero order release kinetics over a period of, e.g.,at least 7 days, at least 15 days, at least 30 days, at least 45 days,at least 60 days, at least 75 days, or at least 90 days. In otheraspects of this embodiment, a controlled-release device releases ahoneybee repellent or composition disclosed herein with substantiallyzero order release kinetics over a period of between, e.g., about 7 daysto about 30 days, about 15 days to about 45 days, about 30 days to about60 days, about 45 days to about 75 days, or about 60 days to about 90days.

In aspects of this embodiment, a controlled-release device releases ahoneybee repellent or composition disclosed herein with substantiallyfirst order release kinetics over a period of, e.g., about 7 days, about15 days, about 30 days, about 45 days, about 60 days, about 75 days, orabout 90 days. In other aspects of this embodiment, a controlled-releasedevice releases a honeybee repellent or composition disclosed hereinwith substantially first order release kinetics over a period of, e.g.,at least 7 days, at least 15 days, at least 30 days, at least 45 days,at least 60 days, at least 75 days, or at least 90 days. In otheraspects of this embodiment, a controlled-release device releases ahoneybee repellent or composition disclosed herein with substantiallyfirst order release kinetics over a period of between, e.g., about 7days to about 30 days, about 15 days to about 45 days, about 30 days toabout 60 days, about 45 days to about 75 days, or about 60 days to about90 days.

Regardless of the method of application, the amount of a honeybeerepellent disclosed herein used is a repellent effective amount, i.e.,it is an amount sufficient to retard the movement of honeybees to theselected location. In aspects of this embodiment, a honeybee repellentdisclosed herein is applied at a rate of, e.g., about 0.01 mg/m², about0.025 mg/m², about 0.05 mg/m², about 0.075 mg/m², about 0.1 mg/m², about0.25 mg/m², about 0.5 mg/m², about 0.75 mg/m², about 1 mg/m², about 2.5mg/m², about 5 mg/m², about 7.5 mg/m², or about 10 mg/m². In otheraspects of this embodiment, a honeybee repellent disclosed herein isapplied at a rate of, e.g., at least 0.01 mg/m², at least 0.025 mg/m²,at least 0.05 mg/m², at least 0.075 mg/m², at least 0.1 mg/m², at least0.25 mg/m², at least 0.5 mg/m², at least 0.75 mg/m², at least 1 mg/m²,at least 2.5 mg/m², at least 5 mg/m², at least 7.5 mg/m², or at least 10mg/m². In yet other aspects of this embodiment, a honeybee repellentdisclosed herein is applied at a rate of, between e.g., about 0.01 mg/m²to about 10 mg/m², about 0.01 mg/m² to about 1 mg/m², about 0.01 mg/m²to about 0.1 mg/m², about 0.05 mg/m² to about 10 mg/m², about 0.05 mg/m²to about 1 mg/m², about 0.05 mg/m² to about 0.1 mg/m², about 0.05 mg/m²to about 5 mg/m², or about 0.05 mg/m² to about 0.5 mg/m².

Aspects of the present specification may also be described as follows:

-   1. A honeybee repellent that substantially mimics a repellent    chemosensory cue of 2-heptanone, wherein the compound is not    2-heptanone.-   2. The honeybee repellent according to embodiment 1, wherein the    honeybee repellent has a repellent chemosensory cue that is at least    75%, at least 80%, at least 85%, at least 90%, at least 95%, or at    least 97% that of the repellent chemosensory cue of 2-heptanone.-   3. The honeybee repellent according to embodiment 1, wherein the    honeybee repellent has a repellent chemosensory cue that is at least    one-fold, at least two-fold, at least three-fold, at least four    fold, at least five-fold, at least six-fold, at least seven-fold, at    least eight-fold, at least nine-fold, at least 10-fold, at least    20-fold, at least 30-fold, at least 40-fold, at least 50-fold, at    least 60-fold, at least 70-fold, at least 80-fold, at least 90-fold,    at least 100-fold, at least 125-fold, at least 150-fold, at least    175-fold, or at least 200-fold that of the repellent chemosensory    cue of 2-heptanone.-   4. A honeybee repellent having a honeybee repellency activity,    wherein the compound is not 2-heptanone.-   5. The honeybee repellent according to embodiment 4, wherein the    honeybee repellent repels honeybees by at least 10%, at least 15%,    at least 20%, at least 25%, at least 30%, at least 35%, at least    40%, at least 45%, at least 50%, at least 55%, at least 60%, at    least 65%, at least 70%, at least 75%, at least 80%, at least 85%,    at least 90%, or at least 95%, as compared to not having the    honeybee repellent present.-   6. The honeybee repellent according to embodiment 4 or 5, wherein    the honeybee repellent reduces a honeybee interaction with a mammal,    a plant, structure, and/or location.-   7. The honeybee repellent according to any one of embodiments 4-6,    wherein the honeybee repellent reduces a honeybee interaction with a    mammal, a plant, structure, and/or location by at least 10%, at    least 15%, at least 20%, at least 25%, at least 30%, at least 35%,    at least 40%, at least 45%, at least 50%, at least 55%, at least    60%, at least 65%, at least 70%, at least 75%, at least 80%, at    least 85%, at least 90%, or at least 95%.-   8. The honeybee repellent according to any one of embodiments 4-7,    wherein the honeybee repellent reduces an ability of a honeybee to    obtain a meal and/or nectar from a plant.-   9. The honeybee repellent according to any one of embodiments 4-8,    wherein the honeybee repellent reduces an ability of a honeybee to    obtain a meal and/or nectar from a plant by at least 10%, at least    15%, at least 20%, at least 25%, at least 30%, at least 35%, at    least 40%, at least 45%, at least 50%, at least 55%, at least 60%,    at least 65%, at least 70%, at least 75%, at least 80%, at least    85%, at least 90%, or at least 95%.-   10. The honeybee repellent according to any one of embodiments 1-9,    wherein the honeybee repellent is more stable than 2-heptanone.-   11. The honeybee repellent according to any one of embodiments 1-10,    wherein the honeybee repellent is less volatile than 2-heptanone.-   12. The honeybee repellent according to any one of embodiments 1-11,    wherein the honeybee repellent has a half-life of at least one day,    at least three days, at least five days, at least one week, at least    two weeks, at least three weeks, at least one month, at least two    months, or at least three months.-   13. The honeybee repellent according to embodiments 1-11, wherein    the honeybee repellent has a half-life about one day to about seven    days, about three days to about seven days, about five days to about    seven days, about one week to about four weeks, about two weeks to    about four weeks, about three weeks to about four weeks, about one    month to about four months, about two months to about four months,    or about three months to about four months.-   14. The honeybee repellent according to any one of embodiments 1-13,    wherein the honeybee repellent has a binding affinity for a honeybee    OBP that is substantially the same as the binding affinity of    2-heptanone, wherein the compound is not 2-heptanone.-   15. The honeybee repellent according to any one of embodiments 1-14,    wherein the honeybee repellent has a binding affinity for a honeybee    OBP that is at least 75%, at least 80%, at least 85%, at least 90%,    at least 95%, or at least 97% that of the binding affinity of    2-heptanone for that honeybee OBP-   16. The honeybee repellent according to any one of embodiments 1-15,    wherein the honeybee repellent has a dissociation equilibrium    constant that is greater than the dissociation equilibrium constant    of 2-heptanone for that honeybee OBP by at least one-fold, at least    two-fold, at least three-fold, at least four fold, at least    five-fold, at least six-fold, at least seven-fold, at least    eight-fold, at least nine-fold, at least 10-fold, at least 20-fold,    at least 30-fold, at least 40-fold, at least 50-fold, at least    60-fold, at least 70-fold, at least 80-fold, at least 90-fold, at    least 100-fold, at least 125-fold, at least 150-fold, at least    175-fold, or at least 200-fold.-   17. The honeybee repellent according to any one of embodiments 1-16,    wherein the honeybee repellent has an association rate constant of    less than 1×10⁵ M⁻¹ s⁻¹, less than 1×10⁶ M⁻¹ s⁻¹, less than 1×10⁷    M⁻¹ s⁻¹, or less than 1×10⁸ M⁻¹ s⁻¹.-   18. The honeybee repellent according to any one of embodiments 1-16,    wherein the honeybee repellent has an association rate constant of    more than 1×10⁵ M⁻¹ s⁻¹, more than 1×10⁶ M⁻¹ s⁻¹, more than 1×10⁷    M⁻¹ s⁻¹, or more than 1×10⁸ M⁻¹ s⁻¹.-   19. The honeybee repellent according to any one of embodiments 1-18,    wherein the honeybee repellent has a disassociation rate constant of    less than 1×10⁻³ s⁻¹, less than 1×10⁻⁴ s⁻¹, or less than 1×10⁻⁵ s⁻¹.-   20. The honeybee repellent according to any one of embodiments 1-18,    wherein the honeybee repellent has a disassociation rate constant of    more than 1×10⁻³ s⁻¹, more than 1×10⁻⁴ s⁻¹, or more than 1×10⁻⁵ s⁻¹.-   21. The honeybee repellent according to any one of embodiments 1-20,    wherein the honeybee repellent has an equilibrium disassociation    constant of less than 0.500 nM, less than 0.450 nM, less than 0.400    nM, less than 0.350 nM, less than 0.300 nM, less than 0.250 nM, less    than 0.200 nM, less than 0.150 nM, less than 0.100 nM, or less than    0.050 nM.-   22. The honeybee repellent according to any one of embodiments 1-20,    wherein the honeybee repellent has an equilibrium disassociation    constant of more than 0.500 nM, more than 0.450 nM, more than 0.400    nM, more than 0.350 nM, more than 0.300 nM, more than 0.250 nM, more    than 0.200 nM, more than 0.150 nM, more than 0.100 nM, or more than    0.050 nM.-   23. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula I, formula    Ia, formula Ib, formula Ic, formula Id, formula Ie, formula If,    formula Ig, formula Ih, and/or formula II disclosed herein.-   24. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula II,    formula IIa, formula IIb, formula IIc, formula IId, formula IIe,    formula IIf, formula IIg, formula IIh, and/or formula IIi disclosed    herein.-   25. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula III,    formula IIIa, formula IIIb, formula IIIc, formula IIId, and/or    formula Ille disclosed herein.-   26. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula IV,    formula IVa, formula IVb, formula IVc, formula IVd, formula IVe,    formula IVf, formula IVg, formula IVh, formula IVi, formula IVj,    and/or formula IVk disclosed herein.-   27. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent is an optionally substituted    2-(4-methoxyphenyl)-3-(2-phenylethyl)-1,3-thiazolidin-4-one, an    optionally substituted    5-phenyl-1-(8-quinolinyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-ol,    an optionally substituted    (3-amino-6-phenylthieno[2,3-b]pyridin-2-yl)(phenyl)methanone, an    optionally substituted 2-(4-ethoxy-6-methyl-2-pyrimidinyl)phenol, an    optionally substituted    2-[4-(allyloxy)-6-methyl-2-pyrimidinyl]phenol, an optionally    substituted ethyl    2-[(2,2-dimethylpropanoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate,    an optionally substituted    N-(3,4-dihydro-1(2H)-quinolinylcarbonothioyl)benzamide, or an    optionally substituted    N-[3-(4-methoxyphenyl)-1-methylpropyl]-4-morpholinamine.-   28. The honeybee repellent according to any one of embodiments 1-27,    wherein the honeybee repellent is not n    2-(4-methoxyphenyl)-3-(2-phenylethyl)-1,3-thiazolidin-4-one,    5-phenyl-1-(8-quinolinyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-ol,    (3-amino-6-phenylthieno[2,3-b]pyridin-2-yl)(phenyl)methanone,    2-(4-ethoxy-6-methyl-2-pyrimidinyl)phenol,    2-[4-(allyloxy)-6-methyl-2-pyrimidinyl]phenol, ethyl    2-[(2,2-dimethylpropanoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate,    N-(3,4-dihydro-1(2H)-quinolinylcarbonothioyl)benzamide, or    N-[3-(4-methoxyphenyl)-1-methylpropyl]-4-morpholinamine.-   29. A composition comprising a compound according to any one of    embodiments 1-28.-   30. The composition according to embodiment 29, wherein the    composition comprises a two or more different compound according to    any one of embodiments 1-28, three or more different compound    according to any one of embodiments 1-28, four or more different    compound according to any one of embodiments 1-28, or five or more    different compound according to any one of embodiments 1-28.-   31. The composition according to embodiments 29 and 30, wherein the    composition further comprises a solvent, a wetting agent, an    emulsifying agent, a carrier, a diluent, or a dispersing agent.-   32. The composition according to embodiments 29-31, wherein the    composition is a liquid form or a solid form.-   33. The composition according to embodiments 29-32, wherein the    composition further comprises one or more an adhesive, a solvent, a    wetting agent, an emulsifying agent, a carrier, a diluent, a    dispersing agent an insecticide, a pesticide, a fungicide, a    fertilizer of a micronutrient or macronutrient nature, a herbicide,    a feeding inhibitor, an insect molting inhibitor, an insect mating    inhibitor, an insect maturation inhibitor, a nematocide, a    nutritional or horticultural supplement, a larvicide, a seed, or any    combination thereof.-   34. The composition according to embodiment 33, wherein the    composition further comprises an insecticide.-   35. The composition according to embodiment 34, wherein the    insecticide is an organochlorine, an organophosphate, a carbamate, a    pyrethroid, or a neonicotinoid.-   36. The composition according to embodiment 35, wherein the    neonicotinoid is Acetamiprid, Clothianidin, Imidacloprid,    Nitenpyram, Nithiazine, Thiacloprid, or Thiamethoxam.-   37. A use of a honeybee repellent according to any one of    embodiments 1-28 or a composition according to any one of    embodiments 29-36 to repel a honeybee from a location by applying    the compound or the composition to the location.-   38. A use of a honeybee repellent according to any one embodiments    1-28 or a composition according to any one of embodiments 29-36 to    repel a honeybee from foraging and/or collecting nectar from a    flower of a plant by applying the compound or the composition to the    plant or in a location in the vicinity of the plant.-   39. A use of a honeybee repellent according to any one of    embodiments 1-28 or a composition according to any one of    embodiments 29-36 to repel a honeybee from a structure by applying    the compound or the composition to the structure or in a location in    the vicinity of the structure.-   40. A method of repelling a honeybee from a location, the method    comprising the step of applying a honeybee repellent according to    any one of embodiments 1-28 or a composition according to any one of    embodiments 29-36 to a location, wherein application of the compound    or the composition to the location repels a honeybee from the    location.-   41. A method of repelling a honeybee from a plant, the method    comprising the step of applying a honeybee repellent according to    any one of embodiments 1-28 or a composition according to any one of    embodiments 29-36 to a plant or in a location in the vicinity of the    plant, wherein application of the compound or the composition to the    location repels a honeybee from foraging and/or collecting nectar    from a flower of the treated plant.-   42. A method of repelling a honeybee from a structure, the method    comprising the step of applying a honeybee repellent according to    any one of embodiments 1-28 or a composition according to any one of    embodiments 29-36 to a structure or in a location in the vicinity of    the structure, wherein application of the compound or the    composition to the structure repels a honeybee from the structure.-   43. A seed composition comprising a seed and a honeybee repellent    according to any one of embodiments 1-28 or a composition according    to any one of embodiments 29-36.-   44. A seed composition of embodiment 43, wherein the composition    further comprises one or more of an insecticide, a pesticide, a    fungicide, a fertilizer of a micronutrient or macronutrient nature,    a herbicide, a feeding inhibitor, an insect molting inhibitor, an    insect mating inhibitor, an insect maturation inhibitor, a    nematocide, a nutritional or horticultural supplement, a larvicide,    a seed, or any combination thereof-   45. A device comprising a honeybee repellent according to any one of    embodiments 1-28 or a composition according to any one of    embodiments 29-36.

EXAMPLES

The following non-limiting examples are provided for illustrativepurposes only in order to facilitate a more complete understanding ofthe disclosed subject matter. These examples should not be construed tolimit any of the embodiments described in the present specification,including those pertaining to the compounds, compositions,pharmaceutical kits, methods or uses of repelling honeybees.

Example 1 Testing of Candidate Compounds Using Binding Assay

To identify a honeybee repellent disclosed herein, candidate compoundswere screened based upon the fact that 2-heptanone is an establishedrepellent of bees. 2-heptanone is thought to mediate its behavioralresponse through binding to a specific odorant-binding protein calledOBP2. Therefore compounds that bind OBP2 have the potential to act asodor “mimics” of 2-heptanone. By utilizing a fluorescent-quench,ligand-protein-binding assay, 30,000 compounds from the DIVERSET®library (ChemBridge Corp., San Diego, Calif.), a chemical library, werescreened and over 150 candidate compounds were isolated that bind OBP2(Table 1). Such assays are generally known in the art. See, e.g.,Briand, et al., Ligand-Binding Properties and StructuralCharacterization of a Novel Rat Odorant-Binding Protein Variant, Eur. J.Biochem. 267(10): 3079-3089 (2000); Briand, et al., Ligand Binding andPhysico-Chemical Properties of ASP2, A Recombinant Odorant-BindingProtein From Honeybee (Apis mellifera L.), Eur. J. Biochem. 268(3):752-760 (2001); Briand, et al., Characterization of a ChemosensoryProtein (ASP3c) from Honeybee (Apis mellifera L.) as a Brood PheromoneCarrier, Eur. J. Biochem. 269(18): 4586-4596 (2002), each of which ishereby incorporated by reference in its entirety.

Example 2 Testing of Candidate Compounds Using the PER Assay

To determine whether a living honeybee can recognize a candidatecompound, these compounds were tested using a proboscis extensionresponse (PER) assay using classical conditioning approaches.

Proboscis extension response conditioning is a case of appetitivelearning, in which bees learn to associate odor stimuli with sucrosereward in the laboratory. In this case, bees were conditioned to producea PER to 2-heptanone as the conditioned stimulus and a sugar reward asthe unconditioned stimulus. These trained bees were then exposed to anodor pulse of a candidate compound to test whether a candidate compoundwould also produce a PER. If the candidate compound “mimics” 2-heptanonethen the honeybee will extend its proboscis.

For conditioning procedures, Apis mellifera Carniolan foraging workerhoneybees were obtained from a local apiary (typically 60 bees pershipment). The honeybees were held overnight in insect cages with foodand water freely available, in an environmentally controlled room on alight cycle similar to the ambient cycle at the time of the assay.

For conditioning procedures, all tests were done in an odorant deliveryapparatus set inside a fume hood. The apparatus comprised a set ofopen-ended, horizontal, 3 cm diameter by 10 cm long plastic tubes. Eachtube was designed where a honeybee could be positioned at the distal endof a tube, with the opening at the other end of the tube locatedproximal to an inlet of the fume hood. To deliver an odorant, room airwas pumped by a diaphragm pump through a particle filter via 0.25 inchplastic tubing at approximately 0.7 m/sec. The air flow passes into theheadspace above an odorant (0.5% [v/v]2-heptanone dissolved in odorlesslight paraffin oil) contained in a 100 mL bottle. The headspace air thenpasses through another plastic tube to a manifold of 4-way valves, eachof which was attached near the proximal end of a plastic tube containinga bee. Each bee was exposed separately for a desired time period to theodorant by opening and closing the appropriate valve. When each valvewas closed, the odor was flushed away immediately by the continuous fumehood air stream.

To train a honeybee to respond to a conditioned and unconditionedstimuli, bees were placed, without anesthesia, in individual 1.5 mLmicro-centrifuge holding tubes and held overnight without access to foodor water. The holding tubes containing the starved bees were placed inracks in groups of eight. One rack at a time was placed behind theodorant delivery apparatus so that each bee's head is centered at thedistal end of a horizontal plastic tube. Each bee was exposed to the2-heptanone odorant alone for four seconds, and then while being fed an80% sucrose solution for and additional three seconds. The sucrosesolution was delivered on a piece of saturated filter paper held inforceps. The wet paper was touched to the bee's antennae if the bee didnot immediately extend its proboscis (which usually happens in afraction of a second after the sucrose solution comes near the bee'shead). Positive and negative responses were recorded. A positive PER wasscored when a bee extended its proboscis before the sucrose appeared. Ina typical trial, 48 individual bees were subjected to conditioning. Sixrounds of training were done before testing began, and typically amajority of the bees were successfully conditioned by the second orthird round of training.

After conditioning, honeybees were tested with the candidate compoundsthe same day or on the following day or, most commonly, both. When heldovernight, bees were fed with sucrose and kept in their holding tubes.When tested the day after training, bees were given one or more roundsof conditioning with 2-heptatone to refresh their memories. Candidatecompounds stocks were made at 5% (w/v) in polyoxyethylene octyl phenylether (TRITON® X-100), a non-ionic detergent/surfactant, and stored at4° C. This detergent is similar to substances used as carriers for avariety of commercial pest-control agents, can act as a solvent for bothhydrophilic and hydrophobic substances, and is itself nearly odorless.Test solutions were made fresh daily by mixing stock solutions withwater for a final compound concentration of 0.5%. A solution of 0.5%2-heptanone in paraffin oil was used as a positive control. Both waterand 15% polyoxyethylene octyl phenyl ether (TRITON® X-100) in waterserved as negative controls to eliminate false positives.

For candidate compound testing experiments, a single 3 cm length of 3 cmdiameter plastic tube is positioned horizontally in a holder so that airis drawn through it at about 0.7 m/sec. Holding tubes containing atrained honeybee were positioned in racks as for the conditioningprocedure. The rack was then moved sequentially behind the tube so thateach bee's head was directly behind the rear end of tube for the test.The test compounds and controls were presented on a saturated piece offilter paper held at the front end of the 3 cm tube. Bees in each rackwere exposed sequentially to a given candidate compound or control forfour seconds and the results recorded. After bees were tested with onecompound, the process was repeated for the next candidate compound usinga clean tube and testing implements. The order of testing was randomizedfor each day's test and generally 5-6 different candidate compounds weretested in a single day along with 3 controls. Only bees giving a PERwith 2-heptanone, but not with the negative controls were counted incalculating the percent of bees testing positive to each compound (Table2). Generally about half of the total bees subjected to conditioningexhibited a PER with the 2-heptanone positive control, and only a verysmall number of these respond to the negative controls. If a givencohort of bees were tested for two consecutive days, they were testedwith two separate sets of candidate compounds to maximize the number ofindividual bees tested with each compound. In a few cases where a singlecohort of bees was tested twice with the same compounds. In this case,the results were averaged and the average was used in the calculation ofthe percent of positives. Table 2 shows results from PER assays for 66candidate compounds.

TABLE 2 OBP2 Binding and Proboscis Extension Response (PER) Assay 2-2-heptanone heptanone positive bees OBP2 binding Candidate Compoundpositive testing positive characteristic No. Name bees (n) to compoundof compound 62 N-(3,4-dihydro-1(2H)- 24 23.6% Moderatequinolinylcarbonothioyl)benzamide 632-(4-methoxyphenyl)-3-(2-phenylethyl)-1,3- 24 21.4% Moderatethiazolidin-4-one 64 2-(4-ethoxy-6-methyl-2-pyrimidinyl)phenol 29 21.7%Moderate 65 N-[3-(4-methoxyphenyl)-1-methylpropyl]-4- 29 7.6% Moderatemorpholinamine 69 ethyl 2-[(2,2-dimethylpropanoyl)amino]-4,5,6,7- 246.5% Moderate tetrahydro-1-benzothiophene-3-carboxylate 705-phenyl-1-(8-quinolinyl)-3-(trifluoromethyl)-4,5- 24 19.1% Moderatedihydro-1H-pyrazol-5-ol 76 (3-amino-6-phenylthieno[2,3-b]pyridin-2- 2911.9% Moderate yl)(phenyl)methanone 1042-[4-(allyloxy)-6-methyl-2-pyrimidinyl]phenol >20 27.9% Moderate Low,indicates no detectable binding to OBP2. Moderate, indicates that 50% orless of the compound bound to OBP2. Strong, indicates that 51% or moreof the compound bound to OBP2.

Example 3 Testing of Candidate Compounds Using Choice Test

To determine whether living honeybees will choice to move towards asource of a candidate compound, these compounds will be assayed using achoice test in a free-flight box apparatus.

All tests will be done in a free-flight box apparatus. The apparatuscomprises a 244 cm long×46 cm deep×30 cm high clear plastic boxincluding two equally-sized independent testing chambers, each with 10cm diameter air inlets that admit filtered room air, separated by asmaller central chamber with a screened air outlet to each testingchamber. Air can be pulled through the sealed box via a 10 cm diameterduct from the air outlet using an AQE Fume Fighter 500 fume extractor(BPA Air Quality Solutions, LLC, Charleston, S.C.), which removes thetest odors using activated charcoal and HEPA filters. The box is housedin an environmentally controlled room with overhead illumination timedto correspond to the current ambient light cycle including 2 additionalsets of lights timed to approximate crepuscular lighting conditions. Thebottom of the apparatus will be lined with clean absorbent paper markedwith a 4×9 grid pattern, forming 12 cm×12 cm squares with markedcoordinates.

Apis mellifera Carniolan foraging worker honeybees will be obtained froma local apiary (typically 60 bees per shipment). Thirty honeybees willbe put into each testing chamber and will be allowed to acclimate for 24hours with food and water freely available. At the beginning of eachtest day all food will be removed from the test chamber, but water willbe continually available throughout all tests. For each test,approximately 0.3 g of organic, raw orange blossom honey will be addedto each clean small plastic weigh boat (Cole-Palmer). The honey boatswill be placed in small plastic culture dishes, which will bedistributed in the marked squares in the chambers. The positions of thedishes on the grid for a set of trials was chosen to avoid bees'preferred resting area so that they will have to find the food actively,but the same dish positions will be maintained for a given set oftrials. We will use seven dishes of honey: six to which the bees willhave access and a seventh that will have a screened lid. The honey ineach boat was weighed on an analytical balance before and after thetest, with the screened sample as a control for evaporative loss. Thefume extractor was left off during the experimental trails, and wasturned on to clear the air after the test dishes were covered andremoved from the chamber at the end of each trial.

Based on the observation that bees tend to return to dishes in the sameposition where they have fed before, each set of trials with each groupof bees began with “Pattern Identification” tests to see which disheslose the most weight, reflecting the most feeding. Once bees areconsuming an acceptable amount in 10-15 min, typically in 1-2 trials, aset of test compound trials will begin. The test compound will bepipetted onto pieces of filter paper placed on the dish bottom below theboat containing a fresh, weighed honey sample so that the test compoundwill be inaccessible to the bees. We used 2 μL of a candidate compoundat a concentration of 0.05-0.5%, in Triton X-100 or paraffin oil, oneach of four pieces of filter paper per dish. The test-solution disheswill be set at the same positions as the one or two dishes favored inthe preceding Pattern Identification trial. To eliminate interferencefrom the solvent, the other dishes without the test substance willcontain the same volume of the appropriate solvent on filter papers asthe test solution dishes. The bees will be allowed to feed for 10-15minutes. Bee movements will be recorded by a small, wide-angle digitalvideo camcorder (HD Hero 960; GoPro, Halfmoon Bay, Calif.) placed on atripod in front of the test chamber. The bees will be given a brief restwhile the honey will be weighed and a second test will be begin withfresh dishes, except that the test compound-containing dish or disheswill be placed at whichever positions were most visited in the precedingtest. Tests will be continued until the bees' feeding slowedsignificantly, typically in 2-4 trials. The bees will be then rested for1-3 hours and a subsequent set of trials begun with another PatternIdentification. Tests were performed in both chambers simultaneously,with the same test compounds. Groups of bees can perform as many as ninetests in one day, with an average of about seven on the first day andsomewhat fewer on subsequent days, usually for three days.

To validate the test system, the known honeybee repellent, 2-heptanone,at the concentration used in the PER assays was used as a positivecontrol for repellency. In addition, neroli oil, a component ofcommercial honeybee attractants (swarm lures), will be used as apositive control for an attractant. Lastly, a dish containing food alonewill be used as a control for the components in the solution minus thecandidate compound. Candidate compounds with high PER scores as well ascompounds with lower PER scores will be examined in order to correlatedthe results from the choice test. Using the criterion of reduction offeeding at dishes that are most visited in the preceding test, candidatecompounds with high PER scores attracted honeybees as well as, orbetter, than 2-heptanone as repellents, while weaker performers in thePER assay are generally less effective repellents.

To determine whether a compound has an effect on the bees in the freeflight box, we calculated the likelihood of bees returning to a dishthat they had exhibited a preference for in the immediately precedingexperiment. For each individual experiment, we considered a dish to bepreferred if it was one of the two dishes from which the most honey wasconsumed. If two consecutive experiments were run in which no compoundswere present, bees showed a 47.5% likelihood of returning to a preferreddish. We then calculated the likelihoods of bees returning to theirpreferred dishes with the compounds. These likelihoods were compared tothe control likelihood of 47.5% using the Z-test (alpha=10%), where n isthe total number of tests a honeybee returned to any test dish, nP isthe number of tests a honeybee returned to a preferred test dish and Pis the probability that a honeybee will return to a test dish and iscalculated by dividing nP with n. Table 3 show the results obtained onselected candidate compounds. 2-heptone was used as a positive controlfor a honeybee repellant.

TABLE 3 Choice Test Assay Candidate Compound No. Name n nP P Z-score —2-heptone 510 217 0.425 −2.256 63 2-(4-methoxyphenyl)- 64 32 0.5 0.3943-(2-phenylethyl)- 1,3-thiazolidin-4-one 64 2-(4-ethoxy-6-methyl-2- 5816 0.276 −3.043 pyrimidinyl)phenol 70 5-phenyl-1-(8-quinolinyl)-3- 30 170.567 1.001 (trifluoromethyl)-4,5-dihydro-1H- pyrazol-5-ol CriticalZ-score is 1.282, with a positive value indicative of an attractant anda negative score indicative of a repellant.

Example 4 Use of Honeybee Repellent in Conjunction with Insecticide

This example illustrates how to use a honeybee repellent disclosedherein to repel honeybees from an area where insecticides have also beenapplied in order to reduce honeybee mortality and avoid insecticidecontamination of honey, beeswax, and other hive products.

At the start of a growing season, an almond tree grower delays the useof a nicotine-based insecticide like Clothianidin and Imidacloprid inorder to minimize harmful effects of this insecticide on honeybees whilethese insects enter his almond tree orchards. While gathering nectarfrom the flowers of the almond trees, the honeybees pollinate the trees.Subsequently the grower does apply a nicotine-based insecticide likeClothianidin and Imidacloprid to his orchards. At the same or similartime, the grower also applies a honeybee repellent disclosed herein. Thegrower may periodically apply repellant using the same schedule as thatfor the insecticide, or one based on the half-life of the honeybeerepellent. The grower realizes typical yields of almonds, while at thesame time his neighbor, who is a beekeeper, reports that his beecolonies are healthy and he has harvested an excellent yield of honey.

Example 5 Use of Honeybee Repellent to Increase Yields of Seedless Crops

This example illustrates how to use a honeybee repellent disclosedherein to prevent unwanted pollination of crop plants by honeybees wheresuch pollination reduces the market value due to the resulting seededcrop.

At the start of a growing season, a mandarin orange grower applies anicotine-based insecticide like Clothianidin and Imidacloprid. At thesame or similar time, the grower also applies a honeybee repellentdisclosed herein. The grower may periodically apply repellant using thesame schedule as that for the insecticide, or one based on the half-lifeof the honeybee repellent. The grower realizes excellent yields ofseedless mandarin oranges. A beekeeper nearby reports that his beecolonies are healthy.

Example 6 Use of Honeybee Repellent to Increase Yields of Seedless Crops

This example illustrates how to use a honeybee repellent disclosedherein to prevent unwanted pollination of crop plants by honeybees wheresuch pollination reduces the market value due to the resulting seededcrop.

At the start of a growing season, a tangerine grower applies a honeybeerepellent disclosed herein. The grower may periodically apply therepellant based on its half-life. The grower realizes excellent yieldsof seedless tangerine. A beekeeper nearby reports that his bee coloniesare healthy.

Example 7 Use of Honeybee Repellent to Control Honeybee Presence inOutdoor Area

This example illustrates how to use a honeybee repellent disclosedherein to keep away honeybees from outdoor areas where human activitiesare occurring and would be disrupted by honeybee presence, such as,e.g., an outdoor activity like a sporting event or picnic.

At the start of a Fourth of July picnic, a mother applies a honeybeerepellent disclosed herein in the area where her family is setting uptable and grill. The mother realizes that, unlike previous events ofthis nature, honeybees did not seem to bother her family while they wereeating their lunch.

Example 8 Use of Honeybee Repellent to Control Honeybee Presence inStructure

This example illustrates how to use a honeybee repellent disclosedherein to keep away honeybees from man-made structures in order toprevent infestation of a colony, such as, e.g., a commercial building, ahouse, a shed, or other structure.

A man recently had an exterminator remove a bee colony that establisheda hive inside one of the ways of his house. This was a reoccurringproblem as it had happened three previous two years as well. Afterremoval, the exterminator applied a honeybee repellent disclosed hereinand also explained to the homeowner that he should periodically applythe repellent in order to prevent a further infestation. The homeownerdid as instructed. The next year honeybees did not establish a hive inthe man's house.

In closing, it is to be understood that although aspects of the presentspecification are highlighted by referring to specific embodiments, oneskilled in the art will readily appreciate that these disclosedembodiments are only illustrative of the principles of the subjectmatter disclosed herein. Therefore, it should be understood that thedisclosed subject matter is in no way limited to a particularmethodology, protocol, and/or reagent, etc., described herein. As such,various modifications or changes to or alternative configurations of thedisclosed subject matter can be made in accordance with the teachingsherein without departing from the spirit of the present specification.Lastly, the terminology used herein is for the purpose of describingparticular embodiments only, and is not intended to limit the scope ofthe present invention, which is defined solely by the claims.Accordingly, the present invention is not limited to that precisely asshown and described.

Certain embodiments of the present invention are described herein,including the best mode known to the inventors for carrying out theinvention. Of course, variations on these described embodiments willbecome apparent to those of ordinary skill in the art upon reading theforegoing description. The inventor expects skilled artisans to employsuch variations as appropriate, and the inventors intend for the presentinvention to be practiced otherwise than specifically described herein.Accordingly, this invention includes all modifications and equivalentsof the subject matter recited in the claims appended hereto as permittedby applicable law. Moreover, any combination of the above-describedembodiments in all possible variations thereof is encompassed by theinvention unless otherwise indicated herein or otherwise clearlycontradicted by context.

Groupings of alternative embodiments, elements, or steps of the presentinvention are not to be construed as limitations. Each group member maybe referred to and claimed individually or in any combination with othergroup members disclosed herein. It is anticipated that one or moremembers of a group may be included in, or deleted from, a group forreasons of convenience and/or patentability. When any such inclusion ordeletion occurs, the specification is deemed to contain the group asmodified thus fulfilling the written description of all Markush groupsused in the appended claims.

Unless otherwise indicated, all numbers expressing a characteristic,item, quantity, parameter, property, term, and so forth used in thepresent specification and claims are to be understood as being modifiedin all instances by the term “about.” As used herein, the term “about”means that the characteristic, item, quantity, parameter, property, orterm so qualified encompasses a range of plus or minus ten percent aboveand below the value of the stated characteristic, item, quantity,parameter, property, or term. Accordingly, unless indicated to thecontrary, the numerical parameters set forth in the specification andattached claims are approximations that may vary. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical indication shouldat least be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques. Notwithstandingthat the numerical ranges and values setting forth the broad scope ofthe invention are approximations, the numerical ranges and values setforth in the specific examples are reported as precisely as possible.Any numerical range or value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Recitation of numerical ranges ofvalues herein is merely intended to serve as a shorthand method ofreferring individually to each separate numerical value falling withinthe range. Unless otherwise indicated herein, each individual value of anumerical range is incorporated into the present specification as if itwere individually recited herein.

The terms “a,” “an,” “the” and similar referents used in the context ofdescribing the present invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or exemplarylanguage (e.g., “such as”) provided herein is intended merely to betterilluminate the present invention and does not pose a limitation on thescope of the invention otherwise claimed. No language in the presentspecification should be construed as indicating any non-claimed elementessential to the practice of the invention.

Specific embodiments disclosed herein may be further limited in theclaims using consisting of or consisting essentially of language. Whenused in the claims, whether as filed or added per amendment, thetransition term “consisting of” excludes any element, step, oringredient not specified in the claims. The transition term “consistingessentially of” limits the scope of a claim to the specified materialsor steps and those that do not materially affect the basic and novelcharacteristic(s). Embodiments of the present invention so claimed areinherently or expressly described and enabled herein.

All patents, patent publications, and other publications referenced andidentified in the present specification are individually and expresslyincorporated herein by reference in their entirety for the purpose ofdescribing and disclosing, for example, the compositions andmethodologies described in such publications that might be used inconnection with the present invention. These publications are providedsolely for their disclosure prior to the filing date of the presentapplication. Nothing in this regard should be construed as an admissionthat the inventors are not entitled to antedate such disclosure byvirtue of prior invention or for any other reason. All statements as tothe date or representation as to the contents of these documents isbased on the information available to the applicants and does notconstitute any admission as to the correctness of the dates or contentsof these documents.

1. A honeybee repellent that substantially mimics a repellentchemosensory cue of 2-heptanone, wherein the honeybee repellant has theformula:

wherein: X¹ and X² are each independently N, O or S; R¹, R², and R³ areeach independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆alkynyl; and n is 1 or 2; or

wherein: X¹ and X² are each independently N, O or S; L¹ and L² are eachindependently C₀, C₁-C₆ alkyl, C₁-C₆ alkylene, C₂-C₆ alkenyl, C₂-C₆alkynyl; Ar¹ and Ar² are each independently aryl, heteroaryl,substituted aryl, or substituted heteroaryl; R¹ is H, OH, OOH, O, OO,C(O), C(O)H, C(O)OH, OC(O)O, C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH,C(O)N, OCN, NHC(O)O, CS, C(S)H, OC(S)N, SCN, CNS, (N)C(S), NH, NH₂,NHNH₂, NNN, NN, N(OH), NC, NCO, (N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH,S(O), S(O)₂, S(O)₃, S(O)₂N, aminoalkyl, halide, haloalkenyl,haloalkoxyl, haloalkyl, halogen, trihalomethanesulfonyl,trihalomethanesulfonamido, trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; and n is 1or 2; or

wherein: X¹ is N, O, or S; X², and X³ are each independently C, N, O orS; L¹ and L² are each independently C₀, C₁-C₆ alkyl, C₁-C₆ alkylene,C₂-C₆ alkenyl, C₂-C₆ alkynyl; Ar¹ and Ar² are each independently aryl,heteroaryl, substituted aryl, or substituted heteroaryl; each R¹ and R²are each independently H, OH, OOH, O, OO, C(O), C(O)H, C(O)OH, OC(O)O,C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N, OCN, NHC(O)O, CS, C(S)H,OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN, NN, N(OH), NC, NCO,(N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O), S(O)₂, S(O)₃, S(O)₂N,aminoalkyl, halide, haloalkenyl, haloalkoxyl, haloalkyl, halogen, C(F)₃,C(Cl)₃, C(Br)₃, C(I)₃, trihalomethanesulfonyl,trihalomethanesulfonamido, trihalomethoxy, oxoalkyl, oxyalkyl, C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl, OC₂₋₆ alkenyl, OC₂₋₆alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, or CO₂C₂₋₆ alkynyl; m is 0-3; nis 1 or 2; and a dashed line represents an optional double bond; or

wherein: X¹, and X⁵ are each independently N, O, or S; X², X³, X⁴, andX⁶ are each independently C, N, O or S; L¹ is C₀, C₁-C₆ alkyl, C₁-C₆alkylene, C₂-C₆ alkenyl, C₂-C₆ alkynyl; and Ar¹ and Ar² are eachindependently aryl, heteroaryl, substituted aryl, or substitutedheteroaryl; R¹ and R² are each independently H, OH, OOH, O, OO, C(O),C(O)H, C(O)OH, OC(O)O, C(O)NH₂, C(O)NC(O), C(NH)NH₂, CN, CNH, C(O)N,OCN, NHC(O)O, CS, C(S)H, OC(S)N, SCN, CNS, (N)C(S), NH, NH₂, NHNH₂, NNN,NN, N(OH), NC, NCO, (N)C(O), NCS, (N)C(S), NO, NO₂, NO₃, SH, S(O),S(O)₂, S(O)₃, S(O)₂N, aminoalkyl, halide, haloalkenyl, haloalkoxyl,haloalkyl, halogen, C(F)₃, C(Cl)₃, C(Br)₃, C(I)₃,trihalomethanesulfonyl, trihalomethanesulfonamido, trihalomethoxy,oxoalkyl, oxyalkyl, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, OC₁₋₆ alkyl,OC₂₋₆ alkenyl, OC₂₋₆ alkynyl, CO₂C₁₋₆ alkyl, CO₂C₂₋₆ alkenyl, CO₂C₂₋₆alkynyl, NC₁₋₆ alkyl, NC₂₋₆ alkenyl, NC₂₋₆ alkynyl, N(C₁₋₆ alkyl)₂,N(C₂₋₆ alkenyl)₂, or N(C₂₋₆ alkynyl)₂.
 2. The honeybee repellentaccording to claim 1, wherein the honeybee repellent is an optionallysubstituted 2-(4-methoxyphenyl)-3-(2-phenylethyl)-1,3-thiazolidin-4-one,an optionally substituted5-phenyl-1-(8-quinolinyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-ol,an optionally substituted(3-amino-6-phenylthieno[2,3-b]pyridin-2-yl)(phenyl)methanone, anoptionally substituted 2-(4-ethoxy-6-methyl-2-pyrimidinyl)phenol, anoptionally substituted 2-[4-(allyloxy)-6-methyl-2-pyrimidinyl]phenol, anoptionally substituted ethyl2-[(2,2-dimethylpropanoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate,an optionally substitutedN-(3,4-dihydro-1(2H)-quinolinylcarbonothioyl)benzamide, or an optionallysubstituted N-[3-(4-methoxyphenyl)-1-methylpropyl]-4-morpholinamine. 3.The honeybee repellent according to claim 1, wherein the honeybeerepellent has a binding affinity for a honeybee OBP that issubstantially the same as the binding affinity of 2-heptanone, whereinthe compound is not 2-heptanone.
 4. The honeybee repellent according toclaim 1, wherein the honeybee repellent reduces a honeybee interactionwith a mammal, a plant, structure, and/or location or wherein thehoneybee repellent reduces an ability of a honeybee to obtain a mealand/or nectar from a plant.
 5. A composition comprising a compound asdefined in claim
 1. 6. The composition according to claim 5, wherein thecomposition comprises one or more different compound as defined in claim1, two or more different compound as defined in claim 1, three or moredifferent compound as defined in claim 1, four or more differentcompound as defined in claim 1, or five or more different compound asdefined in claim
 1. 7. The composition according to claim 5, wherein thecomposition further comprises a solvent, a wetting agent, an emulsifyingagent, a carrier, a diluent, or a dispersing agent.
 8. The compositionaccording to claim 5, wherein the composition further comprises one ormore an adhesive, an insecticide, a pesticide, a fungicide, a fertilizerof a micronutrient or macronutrient nature, a herbicide, a feedinginhibitor, an insect molting inhibitor, an insect mating inhibitor, aninsect maturation inhibitor, a nematocide, a nutritional orhorticultural supplement, a larvicide, a seed, or any combinationthereof.
 9. The composition according to claim 8, wherein theinsecticide is an organochlorine, an organophosphate, a carbamate, apyrethroid, or a neonicotinoid.
 10. The composition according to claim8, wherein the neonicotinoid is Acetamiprid, Clothianidin, Imidacloprid,Nitenpyram, Nithiazine, Thiacloprid, or Thiamethoxam.
 11. A method ofrepelling a honeybee from a structure or location, the method comprisingthe step of applying a honeybee repellent as defined in claim 1 to thestructure or the location, wherein application of the honeybee repellentto the structure or the location repels a honeybee from the structure orthe location.
 12. A method of repelling a honeybee from a structure orlocation, the method comprising the step of applying a composition asdefined in claim 5 to the structure or the location, wherein applicationof the composition to the structure or the location repels a honeybeefrom the structure or the location.
 13. A method of repelling a honeybeefrom a plant, the method comprising the step of applying a honeybeerepellent as defined in claim 1 to the plant or in a location in thevicinity of the plant, wherein application of the honeybee repellent tothe plant or the location repels a honeybee from foraging and/orcollecting nectar from a flower of the treated plant or from a flower inthe vicinity of the treated location.
 14. A method of repelling ahoneybee from a plant, the method comprising the step of applying acomposition as defined in claim 5 to the plant or in a location in thevicinity of the plant, wherein application of the honeybee repellent tothe plant or the location repels a honeybee from foraging and/orcollecting nectar from a flower of the treated plant or from a flower inthe vicinity of the treated location.
 15. A seed composition comprisinga seed and a honeybee repellent as defined in Claim
 1. 16. A seedcomposition of claim 15, wherein the composition further comprises oneor more of an insecticide, a pesticide, a fungicide, a fertilizer of amicronutrient or macronutrient nature, a herbicide, a feeding inhibitor,an insect molting inhibitor, an insect mating inhibitor, an insectmaturation inhibitor, a nematocide, a nutritional or horticulturalsupplement, a larvicide, a seed, or any combination thereof
 17. Thecomposition according to claim 16, wherein the insecticide is anorganochlorine, an organophosphate, a carbamate, a pyrethroid, or aneonicotinoid.
 18. The composition according to claim 17, wherein theneonicotinoid is Acetamiprid, Clothianidin, Imidacloprid, Nitenpyram,Nithiazine, Thiacloprid, or Thiamethoxam.
 19. A device comprising ahoneybee repellent as defined in claim
 1. 20. A device comprising ahoneybee repellent as defined in claim 5.